bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novoassembly, characterization, functional annotation and expression patterns of the black tiger shrimp (Penaeus monodon) transcriptome
Authors: Huerlimann Roger , Wade Nicholas M , Gordon Lavinia , Montenegro Juan D , Goodall Jake , McWilliam Sean , Tinning Matthew , Siemering Kirby , Giardina Erika , Donovan Dallas , Sellars Melony J , Cowley Jeff A , Condon Kelly , Coman Greg J , Khatkar Mehar S , Raadsma Herman W , Maes Gregory , Zenger Kyall R , Jerry Dean R 
Published: March 2018

AbstractThe black tiger shrimp (Penaeus monodon) remains the second most widely cultured shrimp species globally. However, issues with disease and domestication have seen production levels stagnate over the past two decades. To help identify innovative solutions needed to resolve bottlenecks hampering the culture of this species, it is important to generate genetic and genomic resources. Towards this aim, we have produced the most complete publicly availableP. monodontranscriptome database to date. The assembly was carried out in multiple assemblers using 2×125 bp HiSeq data from PolyA selected, ribo-depleted RNA extracted from nine adult tissues and eight early life-history stages. In total, approximately 700 million high-quality sequence reads were obtained and assembled into 236,388 clusters. These were then further segregated into 99,203 adult tissue specific clusters, and 58,678 early life-history stage specific clusters. The final transcriptome had a high TransRate score of 0.37, with 88% of all reads successfully mapping back to the transcriptome. BUSCO statistics showed the assembly to be highly complete with low fragmentation, few genes missing, but higher redundancy or transcript duplication (Complete: 98.2% (Duplicated: 51.3%), Fragmented: 0.8%, Missing: 1.0%), and to greatly exceed the completeness of existingP. monodontranscriptomes. While annotation rates were low (approximately 30%), as is typical for a non-model organisms, annotated transcript clusters were successfully mapped to several hundred functional KEGG pathways. To help address the lack of annotation, transcripts were clustered into groups within tissues and early life-history stages, providing initial evidence for their roles in specific tissue functions, or developmental transitions. Additionally, transcripts of shrimp viruses previously not known to occur in Australia were also discovered. We expect the transcriptome to provide an essential resource to investigate the molecular basis of commercially relevant-significant traits inP. monodonand other shrimp species.
The Dynamics and Energy Landscape of DNA Plectoneme Nucleation
Authors: Walker Philipp U. , Vanderlinden Willem , Lipfert Jan 
Published: March 2018

ABSTRACTDNA buckling is the fundamental step for plectoneme nucleation and supercoil dynamics that are critical in the processing of genetic information. Here we systematically quantify DNA buckling dynamics using high-speed magnetic tweezers. Buckling times are ∼10-100 ms and depend exponentially on both applied force and twist. By deconvolving measured time traces with the instrument response, we reconstruct full 2D extension-twist energy landscapes of the buckling transition that reveal an asymmetry between the pre- and post-buckling states and suggest a highly bend transition state conformation.
Utp14 interaction with the Small Subunit Processome
Authors: Black Joshua J. , Wang Zhaohui , Goering Lisa M. , Johnson Arlen W. 
Published: March 2018

AbstractThe SSU Processome (sometimes referred to as 90S) is an early stabile intermediate in the small ribosomal subunit biogenesis pathway of eukaryotes. Progression of the SSU Processome to a pre-40S particle requires a large-scale compaction of the RNA and release of many biogenesis factors. The U3 snoRNA is a primary component of the SSU Processome and hybridizes to the rRNA at multiple locations to organize the structure of the SSU Processome. Thus, release of U3 is prerequisite for the transition to pre-40S. Our lab proposed that the RNA helicase Dhr1 plays a crucial role in the transition by unwinding U3 and that this activity is controlled by the SSU Processome protein Utp14. How Utp14 times the activation of Dhr1 is an open question. Despite being highly conserved, Utp14 contains no recognizable domains, and how Utp14 interacts with the SSU Processome is not well characterized. Here, we used UV crosslinking and analysis of cDNA and yeast two-hybrid interaction to characterize how Utp14 interacts with the pre-ribosome. Moreover, proteomic analysis of SSU particles lacking Utp14 revealed that Utp14 is needed for efficient recruitment of the RNA exosome. Our analysis positions Utp14 to be uniquely poised to communicate the status of assembly of the SSU Processome to Dhr1 and possibly the exosome as well.
Wheat shovelomics II: Revealing relationships between root crown traits and crop growth
Authors: Slack Shaunagh , York Larry M. , Roghazai Yadgar , Lynch Jonathan , Bennett Malcolm , Foulkes John 
Published: March 2018

AbstractOptimization of root system architecture represents an important goal in wheat breeding. Adopting new field methods for root phenotyping is key to delivering this goal. A novel ‘shovelomics’ method was applied for phenotyping root crown traits to characterize the Savannah x Rialto doubled-haploid (DH) population in two field experiments under irrigated and rain-fed conditions. Trait validation was carried out through soil coring on a subset of 14 DH lines and the two parents. We observed that drought reduced grain yield per plant by 21.0%. Under rain-fed conditions, nodal root angle and roots shoot-1 were positively associated with root length density (RLD) at 40-60 cm depth; RLD was also positively correlated with grain yield. Nodal root angle and roots shoot-1 were also positively associated with canopy stay green and grain yield under rain-fed conditions. We conclude that shovelomics is a valuable technique for quantifying genetic variation in nodal root traits in wheat, revealing nodal root angle and root number per shoot provide useful selection criteria in breeding programs aimed at improving drought tolerance in wheat.HighlightNodal root angle and number shoot-1 measured using ‘shovelomics’ were positively associated with root density at depth and yield under drought in a Savanah x Rialto wheat DH population.
Coordinated cerebellar climbing fiber activity signals learned sensorimotor predictions
Authors: Heffley William , Song Eun Young , Xu Ziye , Taylor Benjamin N. , Hughes Mary Anne , McKinney Andrew , Joshua Mati , Hull Court 
Published: March 2018

AbstractThe prevailing model of cerebellar learning states that climbing fibers (CFs) are both driven by, and serve to correct, erroneous motor output. However, this model is grounded largely in studies of behaviors that utilize hardwired neural pathways to link sensory input to motor output. To test whether this model applies to more flexible learning regimes that require arbitrary sensorimotor associations, we have developed a cerebellar-dependent motor learning paradigm compatible with both mesoscale and single dendrite resolution calcium imaging in mice. Here, we find that CFs are preferentially driven by and more time-locked to correctly executed movements and other task parameters that predict reward outcome, exhibiting widespread correlated activity within parasagittal processing zones that is governed by these predictions. Together, such CF activity patterns are well-suited to drive learning by providing predictive instructional input consistent with an unsigned reinforcement learning signal that does not rely exclusively on motor errors.
MoonFit, a minimal interface for fitting ODE dynamical models, bridging simulation by experimentalists and customization by C++ programmers
Authors: Robert Philippe A. , Jönsson Henrik , Meyer-Hermann Michael 
Published: March 2018

AbstractThe modelling of biological systems often consists into differential equation models that need to be fitted to experimental data. During this complex process, the practical experience of the biologist and the theoretical abstraction of the modeller require back-and-forth refinements of the model, design of new experiments and inclusion of more data-points into the fitting procedure. Available optimization interfaces rarely simultaneously allow customizations by the programmer and the capacity for the biologist to perform simulations or optimizations with a simple interface.Here, we provide the C++ code of a graphical user interface based on a user defined minimal C++ ODE model class. The graphical interface allows to perform simulations and optimizations without any knowledge in programming. The code was designed minimal and modular to be easily modified, with maximal freedom to link customized optimization libraries, solver or hand-made scripts. Moonfit is powerful enough to fit and compare models with high dimensionality, multiple datasets, to automatize optimizations, and to perform iterative fittings using data interpolation. We believe this will ease the interaction between modellers and experimental partners.Availability:Moonfit is freely available via c++ source code and accompanying scripts from gitlab.com/Moonfit/MoonLight.
A novel role for the HLH protein Inhibitor of Differentiation 4 (ID4) in the DNA damage response in basal-like breast cancer
Authors: Baker Laura A. , Krisp Christoph , Roden Daniel , Holliday Holly , Wu Sunny Z. , Junankar Simon , Serandour Aurelien A. , Mohammed Hisham , Nair Radhika , Chan Chia-Ling , Yang Jessica , Foreman Nicola , Fitzpatrick Breanna , Sankaranarayanan Geetha , Law Andrew M.K. , Ormandy Chris , Naylor Matthew J. , McFarland Andrea , Simpson Peter T. , Lakhani Sunil , O’Toole Sandra , Selinger Christina , Anderson Lyndal , Samimi Goli , Hacker Neville F. , Kaplan Warren , Carroll Jason S. , Molloy Mark , Swarbrick Alexander 
Published: March 2018

AbstractBasal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of Differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC, through unknown mechanisms. Here, we have defined a molecular mechanism of action for ID4 in BLBC and the related disease highgrade serous ovarian cancer (HGSOV), by combining RIME proteomic analysis and ChIP-Seq mapping of genomic binding sites. Remarkably, these studies have revealed novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage and regulating DNA damage signalling. Clinical analysis demonstrates that ID4 is amplified and overexpressed at a higher frequency inBRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair pathways. These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOV.
Internal gain modulations, but not changes in stimulus contrast, preserve the neural code
Authors: Lee Sangkyun , Park Jiyoung , Smirnakis Stelios M. 
Published: March 2018

AbstractNeurons in primary visual cortex (V1) are strongly modulated both by stimulus contrast and by fluctuations of internal inputs. An important question is whether population codes are preserved under these conditions. Changes in stimulus contrast are thought to leave population codes invariant, whereas the effect of internal gain modulations remains unknown. To address these questions we studied how the direction-of-motion of oriented gratings is encoded in layer 2/3 of mouse V1. Surprisingly, we found that, because contrast gain responses across cells are heterogeneous, a change in contrast alters the information distribution profile across cells leading to the failure of contrast invariance. Remarkably, internal input fluctuations that cause commensurate firing rate modulations at the single-cell level, do respect population code invariance. These observations have important implications for visual information encoding, and argue that the brain strives to maintain the stability of the neural code in the face of fluctuating internal inputs.
Generation of iPSC-Derived Human Peripheral Sensory Neurons Releasing Substance P Elicited by TRPV1 Agonists
Authors: P. Guimarães Marília Zaluar , Vecchi Rodrigo De , Vitória Gabriela , Sochacki Jaroslaw K. , Paulsen Bruna S. , Lima Igor , da Silva Felipe Rodrigues , da Costa Rodrigo F. Madeiro , Breton Lionel , Rehen Stevens K. 
Published: March 2018

AbstractNeural crest stem cells (NCPCs) have been shown to differentiate into various cell types and tissues during embryonic development, including sensory neurons. The few studies addressing the generation of NCPCs and peripheral sensory neurons (PSNs) from human induced Pluripotent Stem Cells (hiPSCs), generated sensory cells without displaying robust activity. Here, we describe an efficient strategy for hiPSCs differentiation into NCPCs and functional PSNs using chemically defined media and factors to achieve efficient differentiation, confirmed by the expression of specific markers. After 10 days hiPSCs differentiated into NCPCs, cells were then maintained in neural induction medium containing defined growth factors for PSNs differentiation, followed by 10 days in neonatal human epidermal keratinocytes-(HEKn-) conditioned medium. We observed a further increase in PSN markers expression and neurites length after conditioned medium treatment. The resulting neurons released substance P (SP) in response to nociceptive agents such as anandamide and resiniferatoxin. Anandamide induced substance P release via activation of TRPV1 and not CB1. Transcriptomic analysis of the PSNs revealed the main dorsal root ganglia (DRG) neuronal markers and a transcriptional profile compatible with C-LTMR. TRPV1 was detected by immunofluorescence and RNA-Seq in multiple experiments. In conclusion, the developed strategy generated PSNs useful for drug screening that could be applied to patient-derived hiPSCs, consisting in a powerful tool to model human diseases in vitro.
Meta-microRNAs as potential noninvasive markers for early diagnosis of Alzheimer’s disease
Authors: Jiang Ning , Ruan Can-Jun , Cheng Xiao-Rui , Wang Lu-Ning , Tan Ji-Ping , Wang Wei-Shan , Liu Fang , Zhou Wen-Xia , Zhang Yong-Xiang 
Published: March 2018

AbstractIntroductionThe aim of this study was to investigate the potential role of a microRNA panel as early diagnostic markers for Alzheimer’s disease (AD).MethodsThe differentially expressed serum microRNAs were screened with microarray among cognitively normal controls (CNC), mild cognitive impairment (MCI), and AD. QRT-PCR assay was applied to evaluate differentially expressed microRNAs with two independent cohorts including 202 participants. Logistic regression model based on microRNA panel was constructed using a training cohort and then validated using an independent cohort.ResultsFirst, four differentially expressed serum microRNAs (let-7g, miR-197, miR-126 and miR-29a) were found, which expressions were positively correlated with mini mental state examination (MMSE) score. Second, a microRNA panel with the four microRNAs demonstrated good diagnostic performance for MCI and AD with 84% and 92% accuracy. Third, when combined with MMSE score, the diagnostic performance of the microRNA panel was further improved.DiscussionBlood microRNAs are potential AD biomarkers that may lead to new diagnostic strategies.
Evolution analysis and expression divergence of the chitinase gene family against Leptosphaeria maculans and Sclerotinia sclerotiorum infection in Brassica napus
Authors: Xu Wen , Zhou Tengsheng , An Bo , Xu Baojiang , Li Genyi 
Published: March 2018

Abstract:Blackleg and sclerotinia stem rot caused by Leptosphaeria maculans and Sclerotinia sclerotiorum respectively are two major diseases in rapeseed worldwide, which cause serious yield losses. Chitinases are pathogenesis-related proteins and play important roles in host resistance to various pathogens and abiotic stress responses. However, a systematic investigation of the chitinase gene family and its expression profile against L. maculans and S. sclerotiorum infection in rapeseed remains elusive. The recent release of assembled genome sequence of rapeseed allowed us to perform a genome-wide identification of the chitinase gene family. In this study, 68 chitinase genes were identified in Brassica napus genome. These genes were divided into five different classes and distributed among 15 chromosomes. Evolutionary analysis indicated that the expansion of the chitinase gene family was mainly attributed to segmental and tandem duplication. Moreover, the expression profiling of the chitinase gene family was investigated using RNA sequencing (RNA-Seq) and the results revealed that some chitinase genes were both induced while the other members exhibit distinct expression in response to L. maculans and S. sclerotiorum infection. This study presents a comprehensive survey of the chitinase gene family in B. napus and provides valuable information for further understanding the functions of the chitinase gene family.
Heterosynaptic Plasticity Determines the Set-Point for Cortical Excitatory-Inhibitory Balance
Authors: Field Rachel E. , D’amour James A. , Tremblay Robin , Miehl Christoph , Rudy Bernardo , Gjorgjieva Julijana , Froemke Robert C. 
Published: March 2018

SummaryExcitation in neural circuits must be carefully controlled by inhibition to regulate information processing and network excitability. During development, cortical inhibitory and excitatory inputs are initially mismatched but become co-tuned or ‘balanced’ with experience. However, little is known about how excitatory-inhibitory balance is defined at most synapses, or the mechanisms for establishing or maintaining this balance at specific set-points. Here we show how coordinated long-term plasticity calibrates populations of excitatory/inhibitory inputs onto mouse auditory cortical pyramidal neurons. Pairing pre- and postsynaptic activity induced plasticity at paired inputs and different forms of heterosynaptic plasticity at the strongest unpaired synapses, which required minutes of activity and dendritic Ca2+ signaling to be computed. Theoretical analyses demonstrated how the relative rate of heterosynaptic plasticity could normalize and stabilize synaptic strengths to achieve any possible excitatory-inhibitory correlation. Thus excitatory-inhibitory balance is dynamic and cell-specific, determined by distinct plasticity rules across multiple excitatory and inhibitory synapses.
Predicting three-dimensional genome organization with chromatin states
Authors: Qi Yifeng , Zhang Bin 
Published: March 2018

ABSTRACTWe introduce a computational model to simulate chromatin structure and dynamics. Starting from one-dimensional genomics and epigenomics data that are available for hundreds of cell types, this model enables de novo prediction of chromatin structures at five-kilo-base resolution. Simulated chromatin structures recapitulate known features of genome organization, including the formation of chromatin loops, topologically associating domains (TADs) and compartments, and are in quantitative agreement with chromosome conformation capture experiments and super-resolution microscopy measurements. Detailed characterization of the predicted structural ensemble reveals the dynamical flexibility of chromatin loops and the presence of cross-talk among neighboring TADs. Analysis of the model’s energy function uncovers distinct mechanisms for chromatin folding at various length scales.
Adaptive landscape of protein variation in human exomes
Authors: Patel Ravi , Sanderford Maxwell D. , Lanham Tamera R. , Tamura Koichiro , Platt Alexander , Glicksberg Benjamin S. , Xu Ke , Dudley Joel T. , Scheinfeldt Laura B. , Kumar Sudhir 
Published: March 2018

AbstractThe human genome contains hundreds of thousands of missense mutations. However, only a handful of these variants are known to be adaptive, which implies that adaptation through protein sequence change is an extremely rare phenomenon in human evolution. Alternatively, existing methods may lack the power to pinpoint adaptive variation. We have developed and applied an Evolutionary Probability Approach (EPA) to discover candidate adaptive polymorphisms (CAPs) through the discordance between allelic evolutionary probabilities and their observed frequencies in human populations. EPA reveals thousands of missense CAPs, which suggest that a large number of previously optimal alleles had experienced a reversal of fortune in the human lineage. We explored non-adaptive mechanisms to explain CAPs, including the effects of demography, mutation rate variability, and negative and positive selective pressures in modern humans. Our analyses suggest that a large proportion of CAP alleles have increased in frequency due to beneficial selection. This conclusion is supported by the facts that a vast majority of adaptive missense variants discovered previously in humans are CAPs, and that hundreds of CAP alleles are protective in genotype-phenotype association data. Our integrated phylogenomic and population genetic EPA approach predicts the existence of thousands of signatures of non-neutral evolution in the human proteome. We expect this collection to be enriched in beneficial variation. EPA approach can be applied to discover candidate adaptive variation in any protein, population, or species for which allele frequency data and reliable multispecies alignments are available.
WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death
Authors: Wan Huida , Wang Qi , Chen Xiuting , Zeng Qiufang , Shao Yanjiao , Fang Houqin , Liao Xun , Li Husong , Liu Minggang , Xu Tian-Le , Li Dali , Liu Minyao , Meng Bo , Tang Bin , Zhang Zhuohua , Liao Lujian 
Published: March 2018

AbstractMutations in the autophagy gene WDR45 cause β-propeller protein-associated neurodegeneration (BPAN); however the molecular and cellular mechanism of the disease process is largely unknown. Here we generated constitutive Wdr45 knockout (KO) mice that displayed cognitive impairments, abnormal synaptic transmission and lesions in hippocampus and basal ganglia. Immunohistochemistry analysis shows loss of neurons in prefrontal cortex and basal ganglion in aged mice, and increased apoptosis in these regions, recapitulating a hallmark of neurodegeneration. Quantitative proteomic analysis shows accumulation of endoplasmic reticulum (ER) proteins in KO mouse. Furthermore, we show that a defect in autophagy results in impaired ER turnover and ER stress. The unfolded protein response (UPR) is elevated through IRE1α and possibly other kinase signaling pathways, and eventually leads to neuronal apoptosis. Suppression of ER stress, or activation of autophagy through inhibition of mTOR pathway rescues neuronal death. Thus, our study not only provides mechanistic insights for BPAN, but also suggests that a defect in macroautophagy machinery leads to impairment in selective organelle autophagy.