bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures
Authors: Parnell Alice E. , Mordhorst Silja , Kemper Florian , Giurrandino Mariacarmela , Prince Josh P. , Schwarzer Nikola J. , Hofer Alexandre , Wohlwend Daniel , Jessen Henning J. , Gerhardt Stefan , Einsle Oliver , Oyston Petra C. F. , Andexer Jennifer N. , Roach Peter L. 
Published: March 2018

Significance
Polyphosphate kinases (PPKs) are involved in many metabolic processes in bacteria, including pathogenic species. As these enzymes are not present in animals, they are a prime target for the development of novel antibiotics. The detailed knowledge of the mechanism of action and structure–function relationships of these enzymes is of utmost importance for the identification and design of new pharmaceutically active compounds and the rational improvement of lead structures. In addition, PPKs use inexpensive and stable polyphosphate as a phosphate donor and phosphorylate nucleoside 5′-mono- as well as 5′-diphosphates. This makes them of special interest for application in ATP regeneration systems, which can be efficiently coupled to ATP-consuming enzymes in environmentally friendly and sustainable biotechnological processes.
Correlation analysis framework for localization-based superresolution microscopy
Authors: Schnitzbauer Joerg , Wang Yina , Zhao Shijie , Bakalar Matthew , Nuwal Tulip , Chen Baohui , Huang Bo 
Published: March 2018

Significance
Correlation analysis is one of the most widely used image-processing methods. In the quantitative analysis of localization-based superresolution images, there still lacks a generalized coordinate-based correlation analysis framework to take full advantage of the superresolution information. We propose a coordinate-based correlation analysis framework for localization-based superresolution microscopy. We mathematically prove that point-point distance distribution is equivalent to pixel-based correlation function. This framework can be easily extended to model the effect of localization uncertainty, to the time domain and other distance definitions. We demonstrated the versatility and advantages of our framework in three applications of superresolution microscopy: model-free image alignment and averaging for structural analysis, spatiotemporal correlation analysis for mapping molecule diffusion, and quantifying spatial relationships between complex structures.
Reconstructing a metazoan genetic pathway with transcriptome-wide epistasis measurements
Authors: Angeles-Albores David , Puckett Robinson Carmie , Williams Brian A. , Wold Barbara J. , Sternberg Paul W. 
Published: March 2018

Significance
Transcriptome profiling quantitatively measures gene expression genome-wide. There is widespread interest in using transcriptomic profiles as phenotypes for epistasis analysis. Though epistasis measurements can be performed using individual transcripts, this results in many scores that must be interpreted independently. We developed a statistic that summarizes these measurements, simplifying analysis. Moreover, epistasis analysis has previously only been performed on cDNA extracted from single cells. We show that whole-organism RNA-sequencing (RNA-seq) can be used to characterize interactions between genes. With the advent of genome engineering, mutants can be created easily in many organisms. Thus, phenotyping is now the rate-limiting step toward reconstructing interaction networks. Our work potentially represents a solution to this problem because RNA-seq is sensitive to a variety of genetic perturbations.
Sign of selection on mutation rate modifiers depends on population size
Authors: Raynes Yevgeniy , Wylie C. Scott , Sniegowski Paul D. , Weinreich Daniel M. 
Published: March 2018

Significance
It has been known since the early days of population genetics that population size plays a critical role in natural selection. In small populations, selection on alleles that intrinsically affect fitness can be overwhelmed by genetic drift, rendering both beneficial and deleterious alleles selectively neutral. In contrast, alleles that increase the genomic mutation rate (mutators) experience indirect selection, which acts not on their fitness effects but on their genomic associations with fitness-affecting alleles. Here, we show that the sign of indirect selection on mutators can change depending on population size. This phenomenon of sign inversion in selective effect reflects a qualitatively distinct role of population size in evolution and may be broadly important in other instances of indirect selection.
Universal linear and nonlinear electrodynamics of a Dirac fluid
Authors: Sun Zhiyuan , Basov Dmitry N. , Fogler Michael M. 
Published: March 2018

Significance
Electrons in pristine solids behave as a hydrodynamic fluid in a certain range of temperatures and frequencies. We show that the response of such a fluid to an electromagnetic field is different from what is predicted by the usual kinetic theory. Certain aspects of this response are universal, for example, a direct relation between the linear and second-order nonlinear optical conductivities. Discovery of this relation enriches our understanding of the light–matter interaction in diverse electron systems and new materials such as graphene.
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation
Authors: Tan I-Li , Wojcinski Alexandre , Rallapalli Harikrishna , Lao Zhimin , Sanghrajka Reeti M. , Stephen Daniel , Volkova Eugenia , Korshunov Andrey , Remke Marc , Taylor Michael D. , Turnbull Daniel H. , Joyner Alexandra L. 
Published: March 2018

Significance
Cerebellar tumor medulloblastoma (MB) is no longer considered a single disease as it has been separated into four subgroups with further subdivisions based on genomic and clinical data. Mechanistic understandings of the stratification within subgroups should allow for better-targeted treatments. We redefined the main cell of origin by showing that granule cell precursors (GCPs) are heterogeneous with molecularly distinct populations based on their location. As a consequence, GCPs respond differentially to two driver mutations, and a subset of GCPs is more susceptible to Sonic hedgehog (SHH) pathway elevation and forms tumors more readily. These results provide insights into the preferential location of human SHH-MBs in the lateral cerebellum and the cellular and genetic factors influencing SHH-MB progression.
Simple mechanosense and response of cilia motion reveal the intrinsic habits of ciliates
Authors: Ohmura Takuya , Nishigami Yukinori , Taniguchi Atsushi , Nonaka Shigenori , Manabe Junichi , Ishikawa Takuji , Ichikawa Masatoshi 
Published: March 2018

Significance
Single-celled microorganisms are important in ecosystems, and their behaviors impact the Earth’s environments. To survive in harsh environments, these organisms frequently act as though exercising discretion. How do they achieve such intelligent behaviors? In this work, we focused on the accumulation of ciliates on solid/fluid interfaces, where they can obtain sufficient nutrients and a stable environment. This phenomenon is not described in the standard hydrodynamics of microswimmers. Our experiment and simulation revealed that simple principles, the anisotropic shape of the cell and the mechanosensing nature of cilia, induce the accumulation of ciliates on solid/fluid interfaces. The contribution of our work is that a simple response of the cellular apparatus and fluid dynamics explain the apparently clever behavior of ciliates.
Blindfold learning of an accurate neural metric
Authors: Gardella Christophe , Marre Olivier , Mora Thierry 
Published: March 2018

Significance
To understand how neural signals code sensory stimuli, most approaches require knowing both the true stimulus and the neural response. The brain, however, only has access to the neural signals put out by sensory organs. How can it learn to relate neural responses to sensory stimuli, especially for responses to which it has never been exposed? Here we show how to solve this problem by building a metric on neural responses such that responses to the same stimulus are close. Although the metric is built with no access to the stimulus, it outperforms all existing metrics in fine discrimination tasks, suggesting a way the brain could make sense of its sensory output.
Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form
Authors: Nelp Micah T. , Kates Patrick A. , Hunt John T. , Newitt John A. , Balog Aaron , Maley Derrick , Zhu Xiao , Abell Lynn , Allentoff Alban , Borzilleri Robert , Lewis Hal A. , Lin Zeyu , Seitz Steven P. , Yan Chunhong , Groves John T. 
Published: March 2018

Significance
Indoleamine 2,3-dioxygenase (IDO1) is a heme protein that catalyzes the dioxygenation of tryptophan. Cells expressing this activity are able to profoundly alter their surrounding environment to suppress the immune response. Cancer cells exploit this pathway to avoid immune-mediated destruction. Through a range of kinetic, structural, and cellular assays, we show that two classes of highly selective inhibitors of IDO1 act by competing with heme binding to apo-IDO1. This shows that IDO1 is dynamically bound to its heme cofactor in what is likely a critical step in the regulation of this enzyme. These results have elucidated a previously undiscovered role for the ubiquitous heme cofactor in immune regulation, and it suggests that other heme proteins in biology may be similarly regulated.
Measuring discursive influence across scholarship
Authors: Gerow Aaron , Hu Yuening , Boyd-Graber Jordan , Blei David M. , Evans James A. 
Published: March 2018

SignificanceScientific and scholarly influence is multifaceted, shifts over time, and varies across disciplines. We present a dynamic topic model to credit documents with influence that shapes future discourse based on their content and contextual features. We trace discursive innovation in scholarship and identify the influence of particular articles along with their authors, affiliations, and journals. In collections of science, social science, and humanities research spanning over a century, our measure helps predict citations and reveals signals that recognize authors who make diverse contributions and whose contributions take longer to be appreciated, allowing us to compensate for bias in citation behavior.
Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria
Authors: Veeramah Krishna R. , Rott Andreas , Groß Melanie , van Dorp Lucy , López Saioa , Kirsanow Karola , Sell Christian , Blöcher Jens , Wegmann Daniel , Link Vivian , Hofmanová Zuzana , Peters Joris , Trautmann Bernd , Gairhos Anja , Haberstroh Jochen , Päffgen Bernd , Hellenthal Garrett , Haas-Gebhard Brigitte , Harbeck Michaela , Burger Joachim 
Published: March 2018

Significance
Many modern European states trace their roots back to a period known as the Migration Period that spans from Late Antiquity to the early Middle Ages. We have conducted the first population-level analysis of people from this era, generating genomic data from 41 graves from archaeological sites in present-day Bavaria in southern Germany mostly dating to around 500 AD. While they are predominantly of northern/central European ancestry, we also find significant evidence for a nonlocal genetic provenance that is highly enriched among resident Early Medieval women, demonstrating artificial skull deformation. We infer that the most likely origin of the majority of these women was southeastern Europe, resolving a debate that has lasted for more than half a century.
Housing versus Treatment First for Supportive Housing Participants with Substance use Disorders: A Comparison of Housing and Public Service use Outcomes
Authors: Hall Gerod , Walters Sarah , Gould Hannah , Lim Sungwoo 
Published: March 2018

Background Homeless persons with substance use disorders (SUD) have high disease risk, poor access to health care, and are frequent users of Medicaid and other social services. Low-demand supportive housing with no prerequisites for treatment or sobriety has been shown to improve housing stability and decrease public service use for chronically homeless persons with serious mental illness (SMI) and chronic medical conditions. The impact of low-demand housing on individuals with SUD but without co-occurring SMI has been little studied. This evaluation compares housing retention and use of crisis public services (jail, emergency department visits, hospitalization, and substance detoxification) between individuals treated and untreated for SUD before move-in to a low-demand supportive housing program in New York City. Methods The authors used matched administrative records for individuals with SUD but no SMI placed in supportive housing during 2007–2012. Participants received SUD treatment ( n = 1425; treated participants) or were not treated ( n = 512; active users) at housing application. Propensity score–weighted regression analyses were used to best estimate the effect of SUD treatment on incarceration, public service utilization, and housing retention. Results Persons not treated for SUD had a significantly longer tenure in supportive housing than treated participants. However, not treated tenants were more likely to be incarcerated. Opioid agonist therapy and older age decreased the risk of housing discharge, whereas detoxification and inpatient SUD treatment increased the risk of discharge. Conclusions Persons with SUD can achieve residential stability in supportive housing that does not require SUD treatment before admission.
Understanding Hypothetical Bias: An Enhanced Meta‐Analysis
Authors: Penn Jerrod M , Hu Wuyang 
Published: March 2018

AbstractThe presence of hypothetical bias (HB) associated with stated preference methods has garnered frequent attention in the broad literature trying to describe and understand human behavior, often seen in environmental valuation, marketing studies, transportation choices, medical research, and others. This study presents an updated meta‐analysis to explore the source of HB and methods to mitigate it. While previous meta‐analysis on this topic often involves a few dozen articles, this analysis includes 131 studies after reviewing over 500 published and unpublished articles. This enables the inclusion of several important factors that have not been investigated before. These include relatively recent willingness to pay elicitation methods such as choice experiments and the Turnbull lower bound estimator. Newly emerged HB reduction techniques such as consequentiality and certainty follow‐up treatments are also included. For explanatory variables that have been examined in previous studies, this analysis does not always report consistent findings. In particular, holding everything constant and contrary to commonly‐held beliefs, the method of auction does not offer much reduction to HB compared to more conventional methods such as a referendum vote. However, choice experiment, cheap talk, consequentiality and certainty follow‐up all significantly contributed to explaining and mitigating the magnitude of HB. These results help practitioners to understand HB's presence and choose appropriate methods for amelioration. The framework established through this study also enables future analyses targeted at understanding variations built upon one or multiple HB mitigation techniques.
The Fukushima Daiichi Nuclear Power Plant accident and school bullying of affected children and adolescents: the need for continuous radiation education
Authors: Sawano Toyoaki , Nishikawa Yoshitaka , Ozaki Akihiko , Leppold Claire , Tsubokura Masaharu 
Published: March 2018

Abstract
The health threats of radiation-release incidents are diverse and long term. In addition to direct radiation effects, it is imperative to manage the indirect effects of radiation such as stigma, prejudice and broader mental health impacts. Six years after the Fukushima Daiichi Nuclear Power Plant accident of March 2011, bullying caused by stigma and prejudice toward evacuees, including children, has become a social problem in Japan. This phenomenon may be associated with the fact that knowledge about radiation has still not reached the general public, and to a potential lack of motivation among Japanese citizens to learn about radiation and bullying. Continuous and sustained education regarding radiation is warranted in order to enhance the general knowledge level about the effects of radiation in Japan after the Fukushima Daiichi Nuclear Power Plant accident, and this education will become an important reference for education after future nuclear disasters.
Suzaku observations of low surface brightness cluster Abell 1631
Authors: Babazaki Yasunori , Mitsuishi Ikuyuki , Ota Naomi , Sasaki Shin , Böhringer Hans , Chon Gayoung , Pratt Gabriel W , Matsumoto Hironori 
Published: March 2018

Abstract
We present analysis results for a nearby galaxy cluster Abell 1631 at z = 0.046 using the X-ray observatory Suzaku. This cluster is categorized as a low X-ray surface brightness cluster. To study the dynamical state of the cluster, we conduct four-pointed Suzaku observations and investigate physical properties of the Mpc-scale hot gas associated with the A 1631 cluster for the first time. Unlike relaxed clusters, the X-ray image shows no strong peak at the center and an irregular morphology. We perform spectral analysis and investigate the radial profiles of the gas temperature, density, and entropy out to approximately 1.5 Mpc in the east, north, west, and south directions by combining with the XMM-Newton data archive. The measured gas density in the central region is relatively low (a few ×10−4 cm−3) at the given temperature (∼2.9 keV) compared with X-ray-selected clusters. The entropy profile and value within the central region (r &lt; 0.1 r200) are found to be flatter and higher (≳400 keV cm2). The observed bolometric luminosity is approximately three times lower than that expected from the luminosity–temperature relation in previous studies of relaxed clusters. These features are also observed in another low surface brightness cluster, Abell 76. The spatial distributions of galaxies and the hot gas appear to be different. The X-ray luminosity is relatively lower than that expected from the velocity dispersion. A post-merger scenario may explain the observed results.
Environmental science and policy: A meta-synthesis of case studies on boundary organizations and spanning processes
Authors: Jensen-Ryan Danielle K , German Laura A 
Published: March 2018

AbstractWe conducted a meta-synthesis of published qualitative articles to better understand how features and strategies of boundary organizations and spanning processes influence whether environmental science was utilized in politically oriented outcomes. Meta-synthesis is a peer-reviewed research technique which is becoming more prolific as disciplines compare qualitative research studies and generalize qualitative knowledge. In this work, thirty-nine published case studies were analysed through a systematic grounded theory approach and thirty-nine structured interviews were performed with authors to validate the results. Overall, forty-seven boundary spanning variables were evaluated using disaggregated statistics to determine correlation with policy outcomes. Our results develop the possibility that successful boundary spanning linkages may be less about utilizing formal boundary organizations and more about fostering the process through which science and policy are intermingled.
Mitochondrial Fusion Suppresses Pancreatic Cancer Growth via Reduced Oxidative Metabolism
Authors: Yu Meifang , Huang Yanqing , Deorukhkar Amit , Fujimoto Tara N. , Govindaraju Suman , Molkentine Jessica M. , Lin Daniel , Kang Ya’an , Koay Eugene J. , Fleming Jason B. , Gupta Sonal , Maitra Anirban , Taniguchi Cullen M. 
Published: March 2018

SummaryPancreatic cancer is a highly lethal disease whose aggressive biology that is driven by mitochondrial oxidative metabolism. Mitochondria normally form a network of fused organelles, but we find that patient-derived and genetically engineered murine pancreatic cancer cells exhibit highly fragmented mitochondria with robust oxygen consumption rates (OCR). When mitochondrial fusion was activated by the genetic or pharmacological inhibition Drp1, the morphology and metabolism of human and murine pancreatic cancer cells more closely resembled that of normal pancreatic epithelial cells. This reduced metabolism was correlated with slower tumor growth, fewer metastases, and enhanced survival in a syngeneic orthotopic model. Similarly, directly activating mitochondrial fusion by overexpression of Mfn2 also reduced tumor growth and metastases. Mitochondrial fusion in pancreatic cancer cells was associated with reduced mitochondrial mass and Complex I expression and function. Thus, these data suggest that enhancing mitochondrial fusion through Drp1 inhibition or enhanced Mfn2 expression or function has strong tumor suppressive activity against pancreatic cancer and may thus represent a highly novel and efficacious therapeutic target.
3D micro-environment regulates NF–κβ dependent adhesion to induce monocyte differentiation
Authors: Bhattacharya Anindita , Agarwal Mahesh , Mukherjee Rachita , Sen Prosenjit , Sinha Deepak Kumar 
Published: March 2018

AbstractDifferentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signalling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. Our findings challenge the notion that adhesion is a result of monocyte differentiation. Rather it’s the adhesion which triggers the differentiation of monocytes. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.Summary statementThis article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.