bluuebunny/crossref_metadata_2025_split huggingface dataset:
An animal-actuated rotational head-fixation system for 2-photon imaging during 2-d navigation
Authors: Voigts Jakob , Harnett Mark T. 
Published: March 2018

AbstractUnderstanding how the biology of the brain gives rise to the computations that drive behavior requires high fidelity, large scale, and subcellular measurements of neural activity. 2-photon microscopy is the primary tool that satisfies these requirements, particularly for measurements during behavior. However, this technique requires rigid head-fixation, constraining the behavioral repertoire of experimental subjects. Increasingly, complex task paradigms are being used to investigate the neural substrates of complex behaviors, including navigation of complex environments, resolving uncertainty between multiple outcomes, integrating unreliable information over time, and/or building internal models of the world. In rodents, planning and decision making processes are often expressed via head and body motion. This produces a significant limitation for head-fixed two-photon imaging. We therefore developed a system that overcomes a major problem of head-fixation: the lack of rotational vestibular input. The system measures rotational strain exerted by mice on the head restraint, which consequently drives a motor, rotating the constraint system and dissipating the strain. This permits mice to rotate their heads in the azimuthal plane with negligible inertia and friction. This stable rotating head-fixation system allows mice to explore physical or virtual 2-D environments. To demonstrate the performance of our system, we conducted 2-photon GCaMP6f imaging in somas and dendrites of pyramidal neurons in mouse retrosplenial cortex. We show that the subcellular resolution of the system’s 2-photon imaging is comparable to that of conventional head-fixed experiments. Additionally, this system allows the attachment of heavy instrumentation to the animal, making it possible to extend the approach to large-scale electrophysiology experiments in the future. Our method enables the use of state-of-the-art imaging techniques while animals perform more complex and naturalistic behaviors than currently possible, with broad potential applications in systems neuroscience.
Chromatin accessibility landscape of articular knee cartilage reveals aberrant enhancer regulation in osteoarthritis
Authors: Liu Ye , Chang Jen-Chien , Hon Chung-Chau , Fukui Naoshi , Tanaka Nobuho , Zhang Zhenya , Michael Lee Ming Ta , Minoda Aki 
Published: March 2018

ABSTRACTBackgroundOsteoarthritis (OA) is a common joint disorder with increasing impact in an aging society; however, there is no cure or effective treatments so far due to lack of sufficient understanding of its pathogenesis. While genome-wide association studies (GWAS) and DNA methylation profiling identified many non-coding loci associated to OA, the interpretation of them remains challenging.MethodsHere, we employed Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) to map the accessible chromatin landscape in articular knee cartilage of OA patients and to identify the chromatin signatures relevant to OA.ResultsWe identified 109,215 accessible chromatin regions in cartilage and 71% of these regions were annotated as enhancers. We found these accessible chromatin regions are enriched for OA GWAS single nucleotide polymorphisms (SNPs) and OA differentially methylated loci, implying their relevance to OA. By linking these enhancers to their potential target genes, we have identified a list of candidate enhancers that may be relevant to OA. Through integration of ATAC-seq data with RNA-seq data, we identified genes that are altered both at epigenomic and transcriptomic levels. These genes are enriched in pathways regulating ossification and mesenchymal stem cell (MSC) differentiation. Consistently, the differentially accessible regions in OA are enriched for mesenchymal stem cell-specific enhancers and motifs of transcription factor families involved in osteoblast differentiation (e.g. bZIP and ETS).ConclusionsThis study marks the first investigation of accessible chromatin landscape on clinically relevant hard tissues and demonstrates how accessible chromatin profiling can provide comprehensive epigenetic information of a disease. Our analyses provide supportive evidence towards the model of endochondral ossification-like cartilage-to-bone conversion in OA knee cartilage, which is consistent with the OA characteristic of thicker subchondral bone. The identified OA-relevant genes and their enhancers may have a translational potential for diagnosis or drug targets.
ACE: A Workbench using Evolutionary Genetic Algorithms for analysing association in TCGA Data
Authors: Gilmore Alan , Savage Kienan I , O’Reilly Paul , Roddy Aideen C , Dunne Philip D , Lawler Mark , McDade Simon S , Waugh David J , McArt Darragh G 
Published: March 2018

AbstractModern methods in generating molecular data have dramatically scaled in recent years, allowing researchers to efficiently acquire large volumes of information. However, this has increased the challenge of recognising interesting patterns within the data. Atlas Correlation Explorer (ACE) is a user-friendly workbench for seeking associations between attributes in the cancer genome atlas (TCGA) database. It allows any combination of clinical and genomic data streams to be selected for searching, and highlights significant correlations within the chosen data. It is based on an evolutionary algorithm which is capable of producing results for very large searches in a short time.
Stimulus-responsive Self-Assembly of Protein-Based Fractals by Computational Design
Authors: Hernández Nancy E. , Hansen William A. , Zhu Denzel , Shea Maria E. , Khalid Marium , Manichev Viacheslav , Putnins Matthew , Chen Muyuan , Dodge Anthony G. , Yang Lu , Marrero-Berríos Ileana , Banal Melissa , Rechani Phillip , Gustafsson Torgny , Feldman Leonard C. , Lee Sang-Hyuk , Wackett Lawrence P. , Dai Wei , Khare Sagar D. 
Published: March 2018

AbstractFractal topologies, which are statistically self-similar over multiple length scales, are pervasive in nature. The recurrence of patterns at increasing length scales in fractal-shaped branched objects, e.g., trees, lungs, and sponges, results in high effective surface areas, and provides key functional advantages, e.g., for molecular trapping and exchange. Mimicking these topologies in designed protein-based assemblies will provide access to novel classes of functional biomaterials for wide ranging applications. Here we describe a computational design approach for the reversible self-assembly of proteins into tunable supramolecular fractal-like topologies in response to phosphorylation. Computationally-guided atomic-resolution modeling of fusions of symmetric, oligomeric proteins with Src homology 2 (SH2) binding domain and its phosphorylatable ligand peptide was used to design iterative branching leading to assembly formation by two enzymes of the atrazine degradation pathway. Structural characterization using various microscopy techniques and Cryo-electron tomography revealed a variety of dendritic, hyperbranched, and sponge-like topologies which are self-similar over three decades (~10nm-10μm) of length scale, in agreement with models from multi-scale computational simulations. Control over assembly topology and formation dynamics is demonstrated. Owing to their sponge-like structure on the nanoscale, fractal assemblies are capable of efficient and phosphorylation-dependent reversible macromolecular capture. The described design framework should enable the construction of a variety of novel, spatiotemporally responsive biomaterials featuring fractal topologies.One Sentence SummaryWe report a computationally-guided bottom up design approach for constructing fractal-shaped protein assemblies for efficient molecular capture.
The Shape of the Bacterial Ribosome Exit Tunnel Affects Cotranslational Protein Folding
Authors: Kudva Renuka , Tian Pengfei , Avila Fatima Pardo , Carroni Marta , Best Robert B. , Bernstein Harris D. , von Heijne Gunnar 
Published: March 2018

AbstractThe E.coli ribosome exit tunnel can accommodate small folded proteins, while larger ones fold outside. It remains unclear, however, to what extent the geometry of the tunnel influences protein folding. Here, using E. coli ribosomes with deletions in loops in proteins uL23 and uL24 that protrude into the tunnel, we investigate how tunnel geometry determines where proteins of different sizes fold. We find that a 29-residue zinc-finger domain normally folding close to the uL23 loop folds deeper in the tunnel in uL23 Δloop ribosomes, while two ~100-residue protein normally folding close to the uL24 loop near the tunnel exit port fold at deeper locations in uL24 Δloop ribosomes, in good agreement with results obtained by coarse-grained molecular dynamics simulations. This supports the idea that cotranslational folding commences once a protein domain reaches a location in the exit tunnel where there is sufficient space to house the folded structure.
Integrated analysis of human transcriptome data for Rett syndrome finds a network of involved genes
Authors: Ehrhart Friederike , Coort Susan L. , Eijssen Lars , Cirillo Elisa , Smeets Eric E. , Sangani Nasim Bahram , Evelo Chris T. , Curfs Leopold M.G. 
Published: March 2018

AbstractRett syndrome (RTT) is a rare disorder causing severe intellectual and physical disability. The cause is a mutation in the gene coding for the methyl-CpG binding protein 2 (MECP2), a multifunctional regulator protein. Purpose of the study was integration and investigation of multiple gene expression profiles in human cells with impaired MECP2 gene to obtain a data-driven insight in downstream effects. Information about changed gene expression was extracted from five previously published studies. We identified a set of genes which are significantly changed not in all but several transcriptomics datasets and were not mentioned in the context of RTT before. Using overrepresentation analysis of molecular pathways and gene ontology we found that these genes are involved in several processes and molecular pathways known to be affected in RTT. Integrating transcription factors we identified a possible link how MECP2 regulates cytoskeleton organization via MEF2C and CAPG. Integrative analysis of omics data and prior knowledge databases is a powerful approach to identify links between mutation and phenotype especially in rare disease research where little data is available.AbbreviationsRett syndrome (RTT), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), fold change (FC), Gene Ontology (GO), EIF (eukaryotic initiation of transcription factor)For genes the symbols according to the HGNC nomenclature were used.
Long-term all-optical interrogation of cortical neurons in awake-behaving non-human primates
Authors: Ju Niansheng , Jiang Rundong , Macknik Stephen L. , Martinez-Conde Susana , Tang Shiming 
Published: March 2018

ABSTRACTWhereas optogenetic techniques have proven successful in their ability to manipulate neuronal populations in species ranging from insects to rodents—with high spatial and temporal fidelity—significant obstacles remain in their application to non-human primates (NHPs). Robust optogenetics-activated behavior and long-term noninvasive monitoring of target neurons, have been challenging in NHPs. Here we present a method for all-optical interrogation (AOI), integrating optical stimulation and simultaneous two-photon imaging of neuronal populations in the primary visual cortex (V1) of awake rhesus macaques. A red-shifted channel-rhodopsin transgene (C1V1) and genetically-encoded calcium indicators (GCaMP5 or GCaMP6s) were delivered by AAVs, and subsequently expressed in V1 neuronal populations for months with high stability. We achieved optogenetic stimulation using both single-photon (1P) activation of neuronal populations and two-photon (2P) activation of single-cells, while simultaneously recording 2P calcium imaging in awake monkeys. Optogenetic manipulations of V1 neuronal populations produced reliable artificial visual percepts. Together, our advances show the feasibility of precise and stable all-optical interrogation of cortical neurons in awake NHPs, which may facilitate broad applications in high-level cognition and pre-clinical testing studies.
Pooled genome-wide CRISPR screening for basal and context-specific fitness gene essentiality inDrosophila cells
Authors: Viswanatha Raghuvir , Li Zhongchi , Hu Yanhui , Perrimon Norbert 
Published: March 2018

AbstractGenome-wide screens inDrosophilacells have offered numerous insights into gene function, yet a major limitation has been the inability to stably deliver large multiplexed DNA libraries to cultured cells allowing barcoded pooled screens. Here, we developed a site-specific integration strategy for library delivery and performed a genome-wide CRISPR knockout screen inDrosophilaS2R+ cells. Under basal growth conditions, 1235 genes were essential for cell fitness at a false-discovery rate of 5%, representing the highest-resolution fitness gene set yet assembled forDrosophila, including 407 genes which likely duplicated along the vertebrate lineage and whose orthologs were underrepresented in human CRISPR screens. We additionally performed context-specific fitness screens for resistance to or synergy with trametinib, a Ras/ERK/ETS inhibitor, or rapamycin, an mTOR inhibitor, and identified key regulators of each pathway. The results present a novel, scalable, and versatile platform for functional genomic screens in low-redundancy animal cells.
Rapid preimplantation genetic screening (PGS) using a handheld, nanopore-based, DNA sequencer
Authors: Wei Shan , Weiss Zachary R. , Gaur Pallavi , Forman Eric , Williams Zev 
Published: March 2018

AbstractObjectiveTo determine if a handheld, nanopore-based DNA sequencer can be used for rapid preimplantation genetic screening (PGS).DesignRetrospective study.SettingAcademic medical center.Patient(s)Amplified genomic DNA from euploid and aneuploid trophectoderm biopsy samples (n=9) that was also tested using traditional next generation sequencing (NGS).Intervention(s)Short-read DNA library preparation and nanopore-based sequencing using a hand-held MinION sequencer.Main outcome measure(s)Comparison of cytogenetic testing result from NGS and nanopore-based sequencing and the time required for library preparation and sequencing.Result(s)Multiplexed short-read DNA library preparation was completed in 45 minutes. Sequencing times varied from 1 to 2 hours. These times compare favorably with NGS library preparation (>3.5 hours) and sequencing (>12 hours) times. Whole-chromosome aneuploidy screening results obtained from nanopore-based sequencing were identical to those obtained using NGS.Conclusion(s)Methods for PGS of embryos have evolved from FISH to microarrays and most recently to NGS. Here we report the first application of nanopore-based sequencing for PGS on trophecoderm biopsy samples using a rapid multiplex short-read nanopore sequencing library preparation. Aneuploidy screening could be performed on 5 samples in one nanopore flowcell with 1 to 2 hour sequencing times. Overall, nanopore sequencing is a promising tool to perform rapid PGS assay onsite with a rapid turnover time, enabling same day testing and embryo transfer thus obviating the need for complex, large and expensive DNA sequencers or frozen embryos.
Identifying the optimal level of gold as a reserve asset using Black–Litterman model
Authors: Bayram Kamola , Abdullah Adam , Meera Ahamed Kameel 
Published: March 2018

Purpose
After the collapse of the Bretton Woods fixed exchange rate system in 1971, countries moved towards floating exchange rates, and the expectation was that the requirement for foreign reserves would decrease. However, central banks currently hold more foreign exchange reserves to enhance the credibility of exchange rate policies. The demand for gold, which was the main reserve asset prior the collapse of the Bretton Woods system, has increased as a reserve asset once again following the global financial crisis (GFC) of 2008, given gold’s characteristics as a safe haven asset and a store of value. This study aims to analyse official reserves of four countries, namely, Malaysia, Turkey, KSA and Pakistan. The Black–Litterman model was used to build a new strategic portfolio with optimal allocation to gold. This study shows that all countries under the analyses should increase their gold holdings to preserve the value of the portfolio during times of financial turmoil.

Design/methodology/approach
The Black–Litterman model has been used to build a new strategic portfolio with optimal allocation to gold. The study shows that all countries in our analyses suggested increasing their gold holdings to preserve the value of the portfolio during times of financial turmoil.

Findings
The study found that countries under the analyses, namely, Turkey, Malaysia, KSA and Pakistan, suggested increasing their official gold holding given the outstanding performance of gold during the GFC.

Research limitations/implications
Research can be further extended by including few more countries from Organisation of Islamic Cooperation such as Qatar and Indonesia.

Originality/value
Emerging economies such as China, India and Russia started to sharply increase their official gold holdings in the aftermath of the GFC. According to recent statistics, central banks of China and Russia have been adding to their gold reserves. Of note, only in few European countries and in the USA, is the share of gold in foreign reserves more than 50%. In the rest of the world, this figure is about 3-5%. The paper elaborates the aforementioned subject and suggests the strategic weight of gold reserve for each country under analysis.
Imperfect labor mobility and the trickle-down effect in international trade
Authors: Hong Sungwan , Oh Soo Hyun , Sim Seung-Gyu 
Published: March 2018

Purpose
Unlike the common belief in the so-called “trickle-down effect,” trade-induced output growth in a small open economy does not necessarily improve the domestic welfare of the economy. The purpose of this paper is to analyze the conditions under which the trickle-down effect does not work properly such that the connection between trade-induced output growth and welfare improvement is broken.

Design/methodology/approach
This paper introduces an inter-sectoral migration barrier in the general equilibrium model and conducts various simulation experiments under reasonable parameter values.

Findings
This paper demonstrates that subsidizing export industries may raise the total value-added of an economy but deteriorate aggregate welfare. This worsens especially when the supply of non-tradable domestic goods is inelastic, and the demand for them is more substitutable by tradable goods.

Practical implications
To reinforce the trickle-down effect, it is necessary to facilitate efficient labor reallocation and to induce capitalization in the non-tradable sector.

Originality/value
That output growth and welfare improvement do not always move in the same direction requires a reappraisal of the former common belief on the trickle-down effect which emphasizes output growth as an indicator of welfare improvement.
Ecological determinants of avian malaria infections: An integrative analysis at landscape, mosquito and vertebrate community levels
Authors: Ferraguti Martina , Martínez‐de la Puente Josué , Bensch Staffan , Roiz David , Ruiz Santigo , Viana Duarte S. , Soriguer Ramón C. , Figuerola Jordi 
Published: March 2018

Abstract

Vector and host communities, as well as habitat characteristics, may have important but different impacts on the prevalence, richness and evenness of vector‐borne parasites.

We investigated the relative importance of (1) the mosquito community composition, (2) the vertebrate community composition and (3) landscape characteristics on the prevalence, richness and evenness of avian Plasmodium. We hypothesized that parasite prevalence will be more affected by vector‐related parameters, while host parameters should be also important to explain Plasmodium richness and evenness.

We sampled 2,588 wild house sparrows (Passer domesticus) and 340,829 mosquitoes, and we performed vertebrate censuses at 45 localities in the Southwest of Spain. These localities included urban, rural and natural landscapes that were characterized by several habitat variables.

Twelve Plasmodium lineages were identified in house sparrows corresponding to three major clades. Variation partitioning showed that landscape characteristics explained the highest fraction of variation in all response variables (21.0%–44.8%). Plasmodium prevalence was in addition explained by vector‐related variables (5.4%) and its interaction with landscape (10.2%). Parasite richness and evenness were mostly explained by vertebrate community‐related variables.

The structuring role of landscape characteristics in vector and host communities was a key factor in determining parasite prevalence, richness and evenness, although the role of each factor differed according to the parasite parameters studied. These results show that the biotic and abiotic contexts are important to explain the transmission dynamics of mosquito‐borne pathogens in the wild.
Cervical dilatation over time is a poor predictor of severe adverse birth outcomes: a diagnostic accuracy study
Authors: Souza JP , Oladapo OT , Fawole B , Mugerwa K , Reis R , Barbosa‐Junior F , Oliveira‐Ciabati L , Alves D , Gülmezoglu AM 
Published: March 2018

ObjectiveTo assess the accuracy of the World Health Organization (WHO) partograph alert line and other candidate predictors in the identification of women at risk of developing severe adverse birth outcomes.DesignA facility‐based, multicentre, prospective cohort study.SettingThirteen maternity hospitals located in Nigeria and Uganda.PopulationA total of 9995 women with spontaneous onset of labour presenting at cervical dilatation of ≤6 cm or undergoing induction of labour.MethodsResearch assistants collected data on sociodemographic, anthropometric, obstetric, and medical characteristics of study participants at hospital admission, multiple assessments during labour, and interventions during labour and childbirth. The alert line and action line, intrapartum monitoring parameters, and customised labour curves were assessed using sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and the J statistic.OutcomesSevere adverse birth outcomes.ResultsThe rate of severe adverse birth outcomes was 2.2% (223 women with severe adverse birth outcomes), the rate of augmentation of labour was 35.1% (3506 women), and the caesarean section rate was 13.2% (1323 women). Forty‐nine percent of women in labour crossed the alert line (4163/8489). All reference labour curves had a diagnostic odds ratio ranging from 1.29 to 1.60. The J statistic was less than 10% for all reference curves.ConclusionsOur findings suggest that labour is an extremely variable phenomenon, and the assessment of cervical dilatation over time is a poor predictor of severe adverse birth outcomes. The validity of a partograph alert line based on the ‘one‐centimetre per hour’ rule should be re‐evaluated.FundingBill & Melinda Gates Foundation, United States Agency for International Development (USAID), UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), and WHO (A65879).Tweetable abstractThe alert line in check: results from a WHO study.