bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASEP: gene-based detection of allele-specific expression in a population by RNA-seq
Authors: Fan Jiaxin , Hu Jian , Xue Chenyi , Zhang Hanrui , Reilly Muredach P. , Xiao Rui , Li Mingyao 
Published: October 2019

ABSTRACTAllele-specific expression (ASE) analysis, which quantifies the relative expression of two alleles in a diploid individual, is a powerful tool for identifying cis-regulated gene expression variations that underlie phenotypic differences among individuals. Existing methods for gene-level ASE detection analyze one individual at a time, therefore wasting shared information across individuals. Failure to accommodate such shared information not only loses power, but also makes it difficult to interpret results across individuals. However, ASE detection across individuals is challenging because the data often include individuals that are either heterozygous or homozygous for the unobserved cis-regulatory SNP, leading to heterogeneity in ASE as only those heterozygous individuals are informative for ASE, whereas those homozygous individuals have balanced expression. To simultaneously model multi-individual information and account for such heterogeneity, we developed ASEP, a mixture model with subject-specific random effect accounting for multi-SNP correlations within the same gene. ASEP is able to detect gene-level ASE under one condition and differential ASE between two conditions (e.g., pre-versus post-treatment). Extensive simulations have demonstrated the convincing performance of ASEP under a wide range of scenarios. We further applied ASEP to RNA-seq data of human macrophages, and identified genes showing evidence of differential ASE pre-versus post-stimulation, which were extended through findings in cardiometabolic trait-relevant genome-wide association studies. To the best of our knowledge, ASEP is the first method for gene-level ASE detection at the population level. With the growing adoption of RNA-seq, we believe ASEP will be well-suited for various ASE studies for human diseases.
Two-stage electro-mechanical coupling of a KV channel in voltage-dependent activation
Authors: Hou Panpan , Wei Kang Po , Kongmeneck Audrey Deyawe , Yang Nien-Du , Liu Yongfeng , Shi Jingyi , Xu Xianjin , White Kelli McFarland , Zaydman Mark A. , Kasimova Marina A. , Seebohm Guiscard , Zhong Ling , Zou Xiaoqin , Tarek Mounir , Cui Jianmin 
Published: October 2019

AbstractIn voltage-gated potassium (KV) channels, the voltage-sensing domain (VSD) undergoes sequential activation from the resting state to the intermediate state and activated state to trigger pore opening via electro-mechanical (E-M) coupling. However, the spatial and temporal details underlying E-M coupling remain elusive. Here, we leverage KV7.1’s unique two open states associated with the VSD adopting the intermediate and activated conformations to report a two-stage E-M coupling mechanism in voltage-dependent gating of KV7.1 as triggered by VSD activations to the intermediate and then activated state. When the S4 segment transitions to the intermediate state, the hand-like C-terminus of the VSD-pore linker (S4-S5L) interacts with the pore in the same subunit. When S4 then proceeds on to the fully-activated state, the elbow-like hinge between S4 and S4-S5L engages with the pore to activate conductance. This two-stage “hand-and-elbow” gating mechanism elucidates distinct tissue-specific modulations, pharmacology, and disease pathogenesis of KV7.1, and likely applies to numerous KV channels.
Definition of naturally processed peptides reveals convergent presentation of autoantigenic topoisomerase-I epitopes in scleroderma
Authors: Tiniakou Eleni , Fava Andrea , McMahan Zsuzsanna H. , Guhr Tara , O’Meally Robert N. , Shah Ami A. , Wigley Fredrick M. , Cole Robert N. , Boin Francesco , Darrah Erika 
Published: October 2019

AbstractDisease-associatedHLA-DRB1alleles are thought to confer risk of developing autoimmunity by favoring the presentation of select autoantigenic epitopes. However, identification of these epitopes and the principles governing their presentation has been hindered by the imprecision of currently available methods, which cannot fully recapitulate the complexity of human pathophysiology. We present a natural antigen processing assay (NAPA), which overcomes these limitations by studying the presentation of autoantigenic CD4+ T cell epitopes by monocyte-derived dendritic cells (mo-DCs) from patients. We applied this strategy to study the processing and presentation of topoisomerase-1 (TOP1), a prevalent autoantigen in scleroderma that is associated with lung fibrosis and high mortality. We found that a common set of 10 epitopes was presented by mo-DCs from patients with diverse HLA-DR variants, including those not previously associated with the disease. Sequence analysis revealed a shared peptide-binding motif within the HLA-DR peptide binding grooves of patients who developed anti-TOP1 autoantibodies. In addition, a subset of naturally presented TOP1 peptides were characterized by immunological promiscuity, as they could bind to diverse HLA-DR peptide binding grooves. NAPA epitopes were immunorelevant: they could stimulate autoreactive CD4+ T cells in patients, and the number of epitopes recognized correlated with lung disease severity. These findings mechanistically implicate presentation of a convergent set of TOP1 epitopes in the development of scleroderma lung disease. Precise identification of autoantigenic epitopes is key to understanding the primordial mechanisms for the loss of tolerance, studying disease-propagating autoreactive T cells, and developing antigen-specific immunotherapy.One Sentence SummaryUse of a novel natural antigen processing assay reveals a mechanism for the presentation of shared CD4+ T cell epitopes of topoisomerase-I in immunogenetically diverse patients with scleroderma.
High-resolution cryo-EM reconstructions in the presence of substantial aberrations
Authors: Bromberg Raquel , Guo Yirui , Borek Dominika , Otwinowski Zbyszek 
Published: October 2019

The beam-image shift method accelerates data acquisition in cryo-EM single particle reconstruction (cryo-EM SPR) by fast repositioning of the imaging area, but at the cost of more severe and complex optical aberrations.We analyze here how uncorrected anti-symmetric aberrations, such as coma and trefoil, affect cryo-EM SPR results, and then infer an analytical formula quantifying information loss due to their presence that explains why Fourier-shell coefficient (FSC)-based statistics may report significantly overestimated resolution if these aberrations are not fully corrected. We validate our analysis with reference-based aberration refinement for two cryo-EM SPR datasets acquired with a 200 kV microscope in the presence of coma exceeding 40 µm, and obtained 2.3 and 2.7 Å reconstructions for 144 and 173 kDa particles, respectively.Our results provide a description of an efficient approach for assessing information loss in cryo-EM SPR data acquired in the presence of higher-order aberrations and address inconsistent guidelines regarding the level of aberrations acceptable in cryo-EM SPR experiments.
Ensemble cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation
Authors: Johnson Matthew C. , Kollman Justin M. 
Published: October 2019

SummaryInosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. The enzyme is heavily regulated to maintain balance between guanine and adenine nucleotide pools. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand, providing an additional layer of regulatory control associated with increased flux through the guanine synthesis pathway. Here, we report a series of human IMPDH2 cryo-EM structures in active and inactive conformations, and show that the filament resists inhibition by guanine nucleotides. The structures define the mechanism of filament assembly, and reveal how assembly interactions tune the response to guanine inhibition. Filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions, like stem cell proliferation and T-cell activation, that require expansion of guanine nucleotide pools.
Brain Network Constraints and Recurrent Neural Networks reproduce unique Trajectories and State Transitions seen over the span of minutes in resting state fMRI
Authors: Kashyap Amrit , Keilholz Shella 
Published: October 2019

AbstractLarge scale patterns of spontaneous whole brain activity seen in resting state functional Magnetic Resonance Imaging (rsfMRI), are in part believed to arise from neural populations interacting through the structural fiber network [18]. Generative models that simulate this network activity, called Brain Network Models (BNM), are able to reproduce global averaged properties of empirical rsfMRI activity such as functional connectivity (FC) [7, 27]. However, they perform poorly in reproducing unique trajectories and state transitions that are observed over the span of minutes in whole brain data [20]. At very short timescales between measurements, it is not known how much of the variance these BNM can explain because they are not currently synchronized with the measured rsfMRI. We demonstrate that by solving for the initial conditions of BNM from an observed data point using Recurrent Neural Networks (RNN) and integrating it to predict the next time step, the trained network can explain large amounts of variance for the 5 subsequent time points of unseen future trajectory. The RNN and BNM combined system essentially models the network component of rsfMRI, and where future activity is solely based on previous neural activity propagated through the structural network. Longer instantiations of this generative model simulated over the span of minutes can reproduce average FC and the 1/f power spectrum from 0.01 to 0.3 Hz seen in fMRI. Simulated data also contain interesting resting state dynamics, such as unique repeating trajectories, called QPPs [22] that are highly correlated to the empirical trajectory which spans over 20 seconds. Moreover, it exhibits complex states and transitions as seen using k-Means analysis on windowed FC matrices [1]. This suggests that by combining BNMs with RNN to accurately predict future resting state activity at short timescales, it is learning the manifold of the network dynamics, allowing it to simulate complex resting state trajectories at longer time scales. We believe that our technique will be useful in understanding the large-scale functional organization of the brain and how different BNMs recapitulate different aspects of the system dynamics.
Whole genome sequencing of 358 brown planthoppers uncovers the landscape of their migration and dispersal worldwide
Authors: Hu Qing-ling , Zhuo Ji-Chong , Ye Yu-Xuan , Li Dan-Ting , Lou Yi-Han , Zhang Xiao-Ya , Chen Xuan , Wang Si-Liang , Wang Zhe-Chao , Lu Jia-Bao , Mazlan Norida , Nguyen Huy Chung , San OO San , Thet Thet , Sharma Prem Nidhi , Jauharlina Jauharlina , Mizanur Rahman S.M. , Ansari Naved Ahmad , Chen Ai-Dong , Zhu Zeng-Rong , Heong Kong Luen , Cheng Jia-An , Zhan Shuai , Zhang Chuan-Xi 
Published: October 2019

AbstractThe brown planthopper (BPH), Nilaparvata lugens, is a serious migratory rice pest, which is distributed in the broad area of the tropical and temperate Asian-Pacific region. However, we know little about key aspects regarding its evolution such as how they diverged and dispersed worldwide. By resequencing and analyzing 358 BPH genomes from 92 populations across the world, we uncover the genetic relationships among their worldwide populations and the history of their global dispersal. We recovered five genetic groups representing the major population structures. Of these, Australian BPHs were shown large genetic divergence with Asian BPHs; two distinct groups have formed in South and Southeast/East Asia that show strong genetic admixture in the southwest border regions of China and west Thailand with Myanmar; two local populations in Bangladesh and Fujian province of China, respectively, unexpectedly separated with surrounding populations. We also find the genetic similarity and closely phylogenetic relationships between majority of East Asian BPHs and Indo-china peninsula BPHs, indicating that Southeast Asia mainland is the major insect sources and overwintering sites for East Asia. Our study provides important molecular evidence to address BPH evolution and other key aspects of its biology such as insecticides resistance and rice varieties virulence.
Extracting Super-resolution Structures inside a Single Molecule or Overlapped Molecules from One Blurred Image
Authors: Sheffield Edward Y. 
Published: October 2019

AbstractIn some super-resolution techniques, adjacent points are illuminated at different times. Thereby, their locations and light intensities can be detected even if the images are very blurred due to diffraction. According to conventional theories, the points’ inner details cannot be recovered because the images’ high frequency components are removed due to the diffraction-limit. But this study finds an exception, and full information can be extracted from a diffraction-blurred image. In such a “resolvable condition”, neither profile nor detail information is damaged by diffraction. Thereby, it can be recovered reversibly by solving equation systems in spatial domain or frequency domain. This condition is tightly relevant to the imaging condition of existing super-resolution techniques. Based on the condition, a method is proposed which can achieve unlimited high resolutions in principle, and its effectiveness is demonstrated by both theoretical analysis and simulation experiments. It can also work without any observed image outside the region of interest. Simulation experiments also show its tolerance to certain level of noise.
Validating a screening agar for linezolid-resistant enterococci
Authors: Werner Guido , Fleige Carola , Klare Ingo , Weber Robert E. , Bender Jennifer K. 
Published: October 2019

AbstractLinezolid is an alternative treatment option for infections with multidrug-resistant Gram-positive bacteria including vancomycin-resistant enterococci (VRE). Some countries report an increasing number of isolates with resistance to linezolid. The recent publication of the Commission for Hospital Hygiene in Germany on enterococci/VRE recommends screening for linezolid-resistant enterococci (LRE). However, a suitable selective medium or a genetic test is not available. Our aim was to establish a selective screening agar for LRE detection and validate its application with a comprehensive collection of clinical LRE and linezolid-susceptible enterococci (LSE). We decided to combine the selective power of an enterococcal screening agar with a supplementation of linezolid. Several rounds of analyses with reference, control and test strains pointed towards Enterococcosel agar and a concentration of 2 mg/L linezolid. Finally, we validated our LRE agar with 400 samples sent to our National Reference Centre in 2019.
Hox gene expression during the development of the phoronidPhoronopsis harmeri
Authors: Gąsiorowski Ludwik , Hejnol Andreas 
Published: October 2019

AbstractBackgroundPhoronida is a small group of marine worm-like suspension feeders, which together with brachiopods and bryozoans form the clade Lophophorata. Although their development is well studied on the morphological level, data regarding gene expression during this process are scarce and restricted to the analysis of relatively few transcription factors. Here we present a description of the expression patterns of Hox genes during the embryonic and larval development of the phoronidPhoronopsis harmeri.ResultsWe identified sequences of 8 Hox genes in the transcriptome ofP. harmeriand determined their expression pattern during embryonic and larval development using whole mountin situhybridization. We found that none of the Hox genes is expressed during embryonic development. Instead their expression is initiated in the later developmental stages, when the larval body is already formed. The Hox genes are expressed in the metasomal sac, posterior mesoderm and junction between midgut and hindgut - structures that represent rudiments of the adult worm, which emerges through the process of drastic metamorphosis. Additionally, two Hox genes are expressed in the posterior telotroch, which develops in the later larval stages.ConclusionsThe lack of Hox gene expression during early development ofP. harmeriindicates that the larval body develops without positional information of the Hox patterning system. Such phenomenon might be a consequence of the evolutionary intercalation of the larval form into an ancestral, direct life cycle of phoronids. Accordingly, the specific actinotrocha larva found only in Phoronida, would represent an evolutionary novelty, for which an alternative molecular mechanism of antrerior-posterior patterning was recruited. Another explanation of the observed Hox gene expression is that the actinotrocha represents a “head larva”, which is composed of the most anterior body region that is devoid of Hox gene expression. This implies that the Hox patterning system is used for the positional information of the trunk rudiments and is, therefore, delayed to the later larval stages. Future investigation on head-specific genes expression is needed to test this hypothesis.
Gene-signatures predict biologically relevant dose-response potencies in phenotypic assays
Authors: Renner Steffen , Bergsdorf Christian , Bouhelal Rochdi , Koziczak-Holbro Magdalena , Marco Amati Andrea , Techer-Etienne Valerie , Flotte Ludivine , Reymann Nicole , Kapur Karen , Hoersch Sebastian , Oakeley Edward J. , Schuffenhauer Ansgar , Gubler Hanspeter , Lounkine Eugen , Farmer Pierre 
Published: October 2019

AbstractMultiplexed gene-signature-based phenotypic assays are increasingly used for the identification and profiling of small molecule-tool compounds and drugs. Here we introduce a method (provided as R-package) for the quantification of the dose-response potency of a gene-signature as EC50and IC50values.Two signaling pathways were used as models to validate our methods: beta-adrenergic agonistic activity on cAMP generation (dedicated dataset generated for this study) and EGFR inhibitory effect on cancer cell viability. In both cases, potencies derived from multi-gene expression data were highly correlated with orthogonal potencies derived from cAMP and cell growth readouts, and superior to potencies derived from single individual genes.Our results show that gene-signature potencies are a novel valid alternative to conventional readouts for compound potency quantification, in particular in scenarios where no other established readouts are available.
Using the eye-tracking method to study consumer online health information search behaviour
Authors: Gwizdka Jacek , Zhang Yan , Dillon Andrew 
Published: October 2019

Purpose
The purpose of this paper is to introduce eye tracking as a method for capturing direct and indirect measures of online human information search behaviour. The unique contribution of eye-tracking data in studying information behaviour is examined in the context of health information research.

Design/methodology/approach
The need for multiple methods of data collection when examining human online health information behaviour is described and summarised. The nature of human eye movements in information use and reading is outlined and the emergence and application of contemporary eye-tracking technology are explained.

Findings
The paper summarises key contributions and insights that eye tracking has provided across multiple studies, with examples of both direct data on fixations and gaze durations as well as theoretical assessments of relevance and knowledge gain.

Originality/value
The paper provides a basic introduction to the application of a unique method for information research in general and online health information search in particular and provides readers with an awareness of how such data are captured and interpreted.
Disaster risk reduction
Authors: Saulnier Dell D. , Green Helen K. , Ismail Rohaida , Chhorvann Chhea , Bin Mohamed Norlen , Waite Thomas D. , Murray Virginia 
Published: October 2019

PurposeThe Sendai Framework for Disaster Risk Reduction 2015–2030 calls for a reduction in disaster mortality, yet measuring mortality remains a challenge due to varying definitions of disaster mortality, the quality, availability and diversity of data sources, generating mortality estimates, and how mortality data are interpreted.Design/methodology/approachThis paper uses five case studies to provide details around some of the complexities involved with measuring disaster mortality and to demonstrate the clear need for accurate disaster mortality data.FindingsThe findings highlight the benefits of combining multiple data sources for accurate mortality estimates, access to interoperable and readily available global, national, regional and local data sets, and creating standardized definitions for direct and indirect mortality for easier attribution of causes of death.Originality/valueCountries should find a method of measuring mortality that works for them and their resources, and for the hazards they face. Combining accurate mortality data and estimates and leadership at all levels can inform policy and actions to reduce disaster mortality, and ultimately strengthen disaster risk reduction in countries for all citizens.
Investigation of heat transfer in porous channels
Authors: Mulla Mohammed Fahimuddin , Badruddin Irfan Anjum , Nik-Ghazali N. , Muhamad Mohammed Ridha , C. Ahamed Saleel , Ganesan Poo Balan 
Published: October 2019

Purpose
This paper aims to investigate the heat transfer in porous channels.

Design/methodology/approach
Finite element method is used to simulate the heat transfer in porous channels.

Findings
The number and width of channels play a key role in determining the heat transfer of the porous channel. The heat transfer is higher around the channel legs. Smaller base height is better to get higher heat transfer capability.

Originality/value
This study represents the original work to investigate heat transfer in a porous domain having multiple channels.
Reliability of Build Back Better at enhancing resilience of communities
Authors: Vahanvati Mittul , Rafliana Irina 
Published: October 2019

PurposeThe purpose of this study is to analyse the reliability of Build Back Better slogan in the context of post-disaster housing reconstruction in developing countries, at enhancing disaster-resilience of housing and its occupants in the long term from socio-ecological systems resilience perspective.Design/methodology/approachA predominantly qualitative methodology and multi-disciplinary case study methodology is adopted to compare long-term outcomes of two post-disaster housing reconstruction interventions: post-2008 Bihar Kosi River floods in India and post-2010 Mentawai earthquake and tsunami in Indonesia.FindingsOut of the nine generalizable findings, two of the most significant findings include giving freedom of choice or human capabilities to the disaster survivors and sustaining capacity development during and beyond the completion of housing reconstruction. These two processes play a significant role in linking reconstruction to resilience in the long term, especially of those living at- risk and poverty.Originality/valueThis paper further advances the current scholarship on overarching long-term impacts of housing reconstruction efforts, based on longitudinal and empirical studies in India and Indonesia. While these findings represent a snapshot of diverse and complex disaster experiences in the developing-world context, the comparison offers insight into how to turn the rhetoric surrounding “owner-driven” or “built back better” into long-term resilience outcomes.