bluuebunny/crossref_metadata_2025 huggingface dataset:
The Case for Free Trade
Authors: Krueger Anne O.
Published: November 2020

Why do economists support free trade?

There is free trade when residents have the same freedom to buy and sell abroad as they do at home. That does not mean that individuals can buy everything without restriction. Items such as narcotics and firearms from...
What’s Wrong with Protection?
Authors: Krueger Anne O.
Published: November 2020

Winston Churchill has often been quoted as saying that “democracy is the worst possible form of government except for all the others.” It might equally be said that “free trade is the worst possible trade policy except for all the others.” Although the logic...
Case Studies of Protection for Manufacturing Industries
Authors: Krueger Anne O.
Published: November 2020

Why look at manufacturing protection?

In Chapter 4, it was seen that free trade would maximize the goods and services available in the nation’s economy and with enough left over to support those who do not gain from free trade. One set...
Trade Remedies
Authors: Krueger Anne O.
Published: November 2020

What are trade remedies?

The term “trade remedies” describes those cases when it is permissible for tariffs to be raised above their bound levels under GATT/WTO rules. As described in Chapter 11, under GATT/WTO auspices members have agreed in MTNs to gain...
Gray Areas
Authors: Krueger Anne O.
Published: November 2020

What are gray areas?

Gray areas are ones in which valid motives for protection against imports exist but in which there is also scope and opportunity for domestic producers to argue for unwarranted protection. Public sympathy with the stated motive (e.g., environmental concerns) or...
Developing Countries
Authors: Krueger Anne O.
Published: November 2020

Are developing countries different?

Prior to the Second World War, there were advanced countries, there were planned economies, including the Soviet Union, and there were very poor countries. Most of the those in the last category were colonies of one of the advanced countries...
The Political Economy of Trade Policy
Authors: Krueger Anne O.
Published: November 2020

What is the political economy of trade policy?

Many government policies have both a political and an economic aspect. That is true of social security, housing policy, farm policy, support for research, and much more. In all of these cases, the economics of the...
Evolution
Authors: Dunbar Robin
Published: November 2020

Evolution is one of the most important processes in life. It not only explains the detailed history of life on earth, but its scope also extends into many aspects of our own contemporary behavior-who we are and how we got to be here, our psychology, our cultures-and greatly impacts modern advancements in medicine and conservation biology. Perhaps its most important claim for science is its ability to provide an overarching framework that integrates the many life sciences into a single unified whole. Yet, evolution-evolutionary biology in particular-has been, and continues to be, regarded with suspicion by many. Understanding how and why evolution works, and what it can tell us, is perhaps the single most important contribution to the public perception of science. This book provides an overview of the basic theory and showcases how widely its consequences reverberate across the life sciences, the social sciences and even the humanities. In this book, Robin Dunbar uses examples drawn from plant life, animals and humans to illustrate these processes. Evolutionary science has important advantages. Most of science deals with the microscopic world that we cannot see and invariably have difficulty understanding, but evolution deals with the macro-world in which we live and move. That invariably makes it much easier for the lay audience to appreciate, understand and enjoy. Evolution: What Everyone Needs to Know® takes a broad approach to evolution, dealing both with the core theory itself and its impact on different aspects of the world we live in, from the iconic debates of the nineteenth century, to viruses and superbugs, to human evolution and behavior.
Evolution and Adaptation
Authors: Dunbar Robin
Published: November 2020

How do species adapt to their environments?

Darwin argued that species became increasingly adapted to their environments as variants (or what we would now call genetic mutants) that exhibited a slightly better fit to their environment survived better and were able to reproduce more successfully....
Albanians
Authors: Judah Tim
Published: November 2020

Although the focus of this book is Kosovo, it is also about the people of the Western Balkans, especially the Albanians and the Serbs, who do not fit neatly into the boundaries of the states that have come to exist today. More than that,...
Kosovo after 1999
Authors: Judah Tim
Published: November 2020

It is impossible to underestimate the chaos of Kosovo in the wake of the war. Albanians streamed back in and Serbs fled, or were ethnically cleansed, from their homes and villages. Some 120,000 houses had either been destroyed or damaged and bridges and other...
Russia’s Annexation of the Crimea and the War in the Donbas
Authors: Yekelchyk Serhy
Published: November 2020

What shared characteristics led the Crimean Peninsula and the Donbas region to become conflict zones?

These two regions are not in immediate geographic proximity to one another. The Donbas, comprising Donetsk and Luhansk provinces, is Ukraine’s easternmost region, bordering on Russia in the north...
Hydrofracking
Authors: Prud'homme Alex
Published: November 2020

Constantly in the news and the subject of much public debate, fracking, as it is known for short, is one of the most promising yet controversial methods of extracting natural gas and oil. Today, 90 percent of natural gas wells use fracking. Though highly effective, the process-which fractures rock with pressurized fluid-has been criticized for polluting land, air, and water, and endangering human health. A timely addition to Oxford's What Everyone Needs to Know series, Hydrofracking tackles this contentious topic, exploring both sides of the debate and providing a clear guide to the science underlying the technique. In concise question-and-answer format, Alex Prud'homme cuts through the maze of opinions and rhetoric to uncover key points, from the economic and political benefits of fracking to the health dangers and negative effects on the environment. Prud'homme offers clear answers to a range of fundamental questions, including: What is fracking fluid? How does it impact water supplies? Who regulates the industry? How much recoverable natural gas exists in the U.S.? What new innovations are on the horizon? Supporters as diverse as President Obama and the conservative billionaire T. Boone Pickens have promoted natural gas as a clean, "21st-century" fuel that will reduce global warming, create jobs, and provide tax revenues, but concerns remain, with environmental activists like Bill McKibben and others leading protests to put an end to fracking as a means of obtaining alternative energy. Prud'homme considers ways to improve methods in the short-term, while also exploring the possibility of transitioning to more sustainable resources-wind, solar, tidal, and perhaps nuclear power-for the long term. Written for general readers, Hydrofracking clearly explains both the complex science of fracking and the equally complex political and economic issues that surround it, giving readers all the information they need to understand what will no doubt remain a contentious issue for years to come.
Overfishing
Authors: Hilborn Ray , Hilborn Ulrike
Published: November 2020

What is overfishing?

Overfishing is harvesting a fish stock so hard that much of the potential food and wealth will largely slip through our fingers. Yield overfishing is the most common. It prevents a population from producing as much sustainable yield as...
Modern Industrial Fisheries Management
Authors: Hilborn Ray , Hilborn Ulrike
Published: November 2020

What is an example of a well-managed fishery?

On September 10, 2009, the Economist published an article on Bluefin tuna and Eastern Bering Sea pollock entitled “A Tale of Two Fisheries: How to Pillage the Oceans Deliberately, and by Accident.” The article...
Reproductive Politics
Authors: Solinger Rickie
Published: November 2020

Reproductive politics is a term coined by feminists in the 1970s to describe contemporary, Roe v. Wade-era power struggles over contraception and abortion, adoption and surrogacy, and other satellite issues. Forty years later, questions of reproductive rights are just as complex--and controversial--as they were then. Focusing mainly on the United States, Reproductive Politics explores the legal, political, religious, social, ethical, and medical dimensions of this hotly contested arena. Tracing the historical roots of reproductive politics up through the present, Rickie Solinger adopts a question-and-answer format to shed light on such questions as: are sex and reproduction “private” or “public” matters? When was abortion criminalized in the United States--and why? What is “abstinence only” sex education? And how is “reproductive politics” a men’s issue as well as a women’s issue? Covering a substantial range of information in an accessible and lively manner, Solinger orients readers and provides the knowledge necessary to enter into dialogue with this important and continually evolving field.
Energy Sources
Authors: Goldemberg José
Published: November 2020

Which are the primary energy sources?

The world′s energy system is very large: in 2008 it amounted to 492 exajoules, corresponding to 11.75 billion tons of oil equivalent (toe). With a population of almost 6.7 billion people, this corresponds approximately to 1.75 toe per...
Renewables
Authors: Goldemberg José
Published: November 2020

What are renewables?

Renewables, by definition, are forms of energy that are not exhaustible, as are fossil fuels. All renewables originate in the Sun and will last as long as the Sun itself. Most of them, such as wind, waves, hydroelectric, solar thermal, and...
Environmental Problems
Authors: Goldemberg José
Published: November 2020

Why are environmental problems so important today?

In a short period (about 150 years after the Industrial Revolution), the environmental impacts, in terms of magnitude, of human activities became comparable to the ones caused by natural effects. Humans have become a force of geological...
Energy Costs
Authors: Goldemberg José
Published: November 2020

What are the costs of energy?

Energy costs across the world depend on a number of factors. Fossil fuels, which are commodities, are priced on the international market, but local conditions determine the costs of renewable energy. For example, wind-generated electricity can be produced...
New Technologies
Authors: Goldemberg José
Published: November 2020

What is cogeneration?

Cogeneration or CHP (combined heat and power) devices allow the simultaneous production of electric and thermal energy in energy systems. They typically recover and use waste heat from a thermal power plant burning coal.

These systems are widely used in Eastern...
The Fed’s Role, Other Domestic Policies, and Conditions Abroad
Authors: Axilrod Stephen H.
Published: November 2020

What policies outside the Fed’s control most influence its policy effectiveness?

With regard to policies that are, like the Fed’s monetary policy, aimed at influencing the economy as a whole, the federal government’s fiscal policy would be at the top of the list. Fiscal...
Species boundaries and phylogeographic patterns in new species ofNannoniscus(Janiroidea: Nannoniscidae) from the equatorial Pacific nodule province inferred from mtDNA and morphology
Authors: Kaiser Stefanie , Kihara Terue Cristina , Brix Saskia , Mohrbeck Inga , Janssen Annika , Jennings Robert M
Published: November 2020

Spatial patterns of genetic variation (based on COI and 16S mtDNA) for morphologically similar species in the isopod genus Nannoniscus G.O. Sars. 1870 were examined that occur broadly across the Clarion Clipperton Fracture Zone (CCZ). Samples were obtained from five different licence areas as well as an Area of Particular Environmental Interest (APEI-6) with sites located at various distances (a few to several hundred kilometres) from one another. Applying three different species delimitation (SD) methods (sGMYC, mPTP and ABGD) of the molecular data, we could distinguish between four and 12 different molecular taxonomic operational units (MOTUs). Morphological analyses could confirm five distinct phenotypic clades that represent species new to science and are described here: Nannoniscus brenkei sp. nov., Nannoniscus hilario sp. nov., Nannoniscus magdae sp. nov., Nannoniscus menoti sp. nov. and Nannoniscus pedro sp. nov. Despite the assumed limited dispersal capacity of Nannoniscus species, we found haplotypes of two species to be geographically widespread (up to > 1400 km apart), as opposed to several divergent clades occurring in close vicinity or even sympatry. Geographic distance appeared to explain the phylogeographic structure of Nannoniscus species to some extent, although oceanographic features and level of environmental heterogeneity were probably equally important.
Mechanisms of Peritoneal Acid-Base Kinetics During Peritoneal Dialysis: A Mathematical Model Study
Authors: Wolf Matthew B.
Published: November 2020

To investigate mechanisms of acid-base changes during peritoneal dialysis (PD), a mathematical model was developed that describes kinetics of peritoneal bicarbonate, CO2, and pH during the dwell with both high and low lactate-containing dialysis fluids. The model was based on a previous modification of the Rippe 3-Pore model of water and solute kinetic transport across the peritoneal membrane during the PD dwell. A central feature of the present modification is an electroneutrality constraint on peritoneal-fluid ion concentrations, which results in the conclusion that peritoneal bicarbonate-concentration kinetics are entirely dependent on the kinetics of the other ions. This new model was able to closely predict peritoneal bicarbonate-concentration kinetics during the dwell. Predictions of total peritoneal bicarbonate-mass kinetics were greater than those of porous, transmembrane bicarbonate transport, suggesting that a portion of bicarbonate comes from CO2 transport, both porous and nonporous and then a partial conversion to bicarbonate. Fitting the model to experimental pH data during the dwell, required addition of a peritoneal CO2 mass-conservation constraint, coupled with the description for peritoneal bicarbonate kinetics. Predicted pH kinetics during the dwell, closely mimicked the experimental data. The conclusion was that the mechanisms describing peritoneal bicarbonate and pH kinetics during PD must include 1) electroneutrality of peritoneal fluid, 2) porous transport of bicarbonate and CO2, 3) nonporous transport of CO2, and 4) CO2 conversion to bicarbonate. These mechanisms are quite different and more complex than the bicarbonate-centered, lactate to acid-generation mechanisms previously proposed.
Pediatric Trauma Arrival Times and the Swing Shift
Authors: Berg Patrick , Chestovich Paul J. , Jones Stephanie , Allenback Gayle , McNickle Allison G. , Saquib Syed F. , Fraser Douglas R. , Kuhls Deborah A.
Published: November 2020

Background

Trauma center staff and trainees are often assigned to a day and night shift. However, for adult trauma, the swing shift has been found to offer superior clinical exposure compared with a standard day or night shift for trainees. We characterized patterns in pediatric trauma arrival times based on the hour, weekday, and month and studied whether or not the swing shift also maximizes exposure to hands-on experiences in managing pediatric trauma.

Methods

We performed a retrospective review of the trauma database at our urban, level 2 pediatric trauma center. We identified all the pediatric trauma activations in the last 13 years (2006–2018). A retrospective shift log was created, which included day (7:00 am to 7:00 pm), night (7:00 pm to 7:00 am), and swing (noon to midnight) shifts. The shifts were compared using the Wilcoxon match-pairs signed rank test. Weekends data were also compared with weekdays, and comparisons were also made for pediatric patients with Injury Severity Scores (ISS) >15.

Results

There were 3532 pediatric patients identified for our study. The swing shift had 1.98 times more activations than the night shift, and 1.33 more than the day shift (P < 0.001). The swing shift was also superior to both the day and night shifts for exposure to patients with Injury Severity Score greater than 15 (P < 0.001). Weekend days had 1.28 times more trauma than the weekdays (P < 0.001). Peak arrival time was between the hours of 3:00 pm and 9:00 pm, and patient age did not have an effect on this trend.

Conclusions

Experience in managing pediatric trauma patients will improve for trainees who utilize the swing shift. In addition, the hours between 3:00 pm and 9:00 pm on weekends may represent a time of particularly high likelihood of pediatric trauma arrivals, which may require extra staff and hospital resources.

Level of Evidence: Therapeutic Study, Level IV
Activity Within an Extraperitoneal Ureteral Herniation Detected on Bone Scan, Associated With a Partially Duplicated Collecting System
Authors: Robbins Robert , Bhat Roopa , Baqar Mohamed , Singh Amolak
Published: November 2020

A 64-year-old man with history of renal stones and prostate cancer presented for evaluation of osseous metastatic disease due to elevated prostate-specific antigen (13.7 ng/mL). A 99mTc-labeled bone scan demonstrated unusual linear uptake projecting over the lower pelvis extending into the scrotum. Follow-up CT confirmed a rare case of inguinoscrotal extraperitoneal herniation of the ureter associated with a partially duplicated left renal collecting system. The left-sided inguinoscrotal uptake was within the herniated ureter, potentially mimicking disease within the pelvis.
Extensive Postchemotherapy Calcinosis Cutis in a Non-Hodgkin Lymphoma Patient With Spontaneous Resolution
Authors: Mishra Vineet , Madurai Kalimuthu Lokeshwaran , Singh Prakash , Ora Manish , Gambhir Sanjay
Published: November 2020

We report the case of a 30-year-old woman with stage IV, non-Hodgkin lymphoma. Baseline 18F-FDG PET/CT scan revealed lymphadenopathy with breasts and skeletal involvement. She received 3 cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) chemotherapy without significant adverse effects. Biochemical examinations before and after chemotherapies were unremarkable. Interim18F-FDG PET/CT showed a partial treatment response. However, there was an appearance of FDG-avid coarse calcification in breasts. Cutaneous and subcutaneous regions of elbows, pelvis, and thighs showed similar calcifications. Posttherapy PET/CT showed a significant resolution of calcinosis cutis. This case presents a postchemotherapy idiopathic calcinosis cutis with rapid spontaneous resolution.
A New Type of Three-Dimensional Customized Composite Implant in Reconstruction of Large Skull Defects
Authors: Huang Qinghua , Yang Bin , Li Binghang , Ma Hengyuan
Published: November 2020

Large skull defects can result in chronic injury to intracranial tissues as well as psychological trauma for patients, and their repair presents a challenge to surgeons. Hydroxyapatite has been used in reconstructing skull defects for many years, but it is difficult to adjust the shape and size of the material intraoperatively, especially for large defects. With three-dimensional digital technology, a new type of customized composite implant made of epoxide acrylate maleic and hydroxyapatite has been applied in clinical practice. In this retrospective review, 15 patients with large skull defects (4 female and 11 male, at a mean age of 36.4 years, range from 24–65 years) were treated with the novel customized composite implant, reconstructing the large skull defects successfully. During the average 2.2 years follow-up period (range 0.5–4 years), complications including infection, cerebrospinal fluid leakage, intracranial hemorrhage, or implant exposurea were not occured, only 1 patient (6.7%) with a seroma managed non-operatively. The customized implants, which required no intraoperative adjustments and are about a third of the cost of titanium implants, are an excellent alternative for large skull defect repair.
Biofilm formation by Bacillus subtilis is altered in the presence of pesticides
Authors: Newton Rachael , Amstutz Jennifer , Patrick Joyce E.
Published: November 2020

Bacillus subtilis

uses swarming motility and biofilm formation to colonize plant roots and form a symbiotic relationship with the plant. Swarming motility and biofilm formation are group behaviours made possible through the use of chemical messengers. We investigated whether chemicals applied to plants would interfere with the swarming motility and biofilm-forming capabilities of B. subtilis in vitro. We hypothesized that pesticides could act as chemical signals that influence bacterial behaviour; this research investigates whether swarming motility and biofilm formation of

B. subtilis

is affected by the application of the commercial pesticides with the active ingredients of neem oil, pyrethrin, or malathion. The results indicate that all three pesticides inhibit biofilm formation. Swarming motility is not affected by the application of pyrethrin or malathion, but swarm expansion and pattern is altered in the presence of neem oil. Future studies to investigate the mechanism by which pesticides alter biofilm formation are warranted.
Steptomyces fagopyri sp. nov., a novel actinomycete isolated from rhizospheric soil of Fagopyrum dibotrys
Authors: Guo Yihui , Tang Xinke , Hu Siren , Li Kaiqin , Zhou Meiliang , Jian Gao
Published: November 2020

A novel actinomycete, designated strain QMT-28T, was isolated from rhizosphere soil of Fagopyrum dibotrys collected from Shuangfeng, Hunan Province, PR China. Strain QMT-28T grew well on International

Streptomyces

Project series media and formed well-developed, branched substrate hyphae and aerial mycelium that differentiated into loose spiral spore chains consisting of cylindrical spores with smooth surfaces. The diagnostic diamino acid was ll-diaminopimelic acid and the whole-cell sugars were galactose and glucose. The predominant fatty acids were C18 : 1
cis9, summed feature 6 (C18 : 2
cis 9,12/C18 : 0 a) and C16 : 0. The polar lipids included diphosphatidylglycerol, hydroxy phospatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides, phospholipids of unknown structure containing glucosamine and several unidentified phospholipids. The major menaquinones were MK-9, MK-9(H2), MK-9(H4), MK-9(H6) and MK-9(H8). The genome size of strain QMT-28T was about 8.7 Mbp with a G+C content of 71.2 mol%. Phylogenetic analysis showed that the novel strain was closely related to

Streptomyces olivochromogenes

DSM 40451T (99.5 % similarity),

Streptomyces mirabilis

NBRC 13450T (98.9 %),

Streptomyces kanamyceticus

NBRC 13414T (98.9 %),

Streptomyces kaempferi

I37T (98.9 %) and

Streptomyces arcticus

ZLN234T (98.8 %). However, the average nucleotide identity values, the digital DNA–DNA hybridization values and the multilocus sequence analysis evolutionary distances between this strain and closely related strains showed that it belonged to a distinct species. In addition, these results were also supported by differences in the phenotypic characteristics between QMT-28T and five closely related type strains. Consequently, strain QMT-28T should represent a novel species of the genus

Streptomyces

, with the suggested name Streptomyces fagopyri sp. nov. The type strain is QMT-28T (=CICC 24808T=JCM 33796T).
Long inverted repeats around the chromosome replication terminus in the model strain Bacillus thuringiensis serovar israelensis BGSC 4Q7
Authors: Bolotin Alexander , Quinquis Benoit , Roume Hugo , Gohar Michel , Lereclus Didier , Sorokin Alexei
Published: November 2020

Bacillus thuringiensis

serovar israelensis is the most widely used natural biopesticide against mosquito larvae worldwide. Its lineage has been actively studied and a plasmid-free strain,

B

.

thuringiensis

serovar israelensis BGSC 4Q7 (4Q7), has been produced. Previous sequencing of the genome of this strain has revealed the persistent presence of a 235 kb extrachromosomal element, pBtic235, which has been shown to be an inducible prophage, although three putative chromosomal prophages have been lost. Moreover, a 492 kb region, potentially including the standard replication terminus, has also been deleted in the 4Q7 strain, indicating an absence of essential genes in this area. We reanalysed the genome coverage distribution of reads for the previously sequenced variant strain, and sequenced two independently maintained samples of the 4Q7 strain. A 553 kb area, close to the 492 kb deletion, was found to be duplicated. This duplication presumably restored the equal sizes of the replichores, and a balanced functioning of replication termination. An analysis of genome assembly graphs revealed a transient association of the host chromosome with the pBtic235 element. This association may play a functional role in the replication of the bacterial chromosome, and the termination of this process in particular. The genome-restructuring events detected may modify the genetic status of cytotoxic or haemolytic toxins, potentially influencing strain virulence. Twelve of the single-nucleotide variants identified in 4Q7 were probably due to the procedure used for strain construction or were present in the precursor of this strain. No sequence variants were found in pBtic235, but the distribution of the corresponding 4Q7 reads indicates a significant difference from counterparts in natural

B. thuringiensis

serovar israelensis strains, suggesting a duplication or over-replication in 4Q7. Thus, the 4Q7 strain is not a pure plasmid-less offshoot, but a highly genetically modified derivative of its natural ancestor. In addition to potentially influencing virulence, genome-restructuring events can modify the replication termination machinery. These findings have potential implications for the conclusions of virulence studies on 4Q7 as a model, but they also raise interesting fundamental questions about the functioning of the

Bacillus

genome.
TNMplot.com: a web tool for the comparison of gene expression in normal, tumor and metastatic tissues
Authors: Bartha Áron , Győrffy Balázs
Published: November 2020

Genes showing higher expression in either tumor or metastatic tissues can help in better understanding tumor formation, and can serve as biomarkers of progression or as therapy targets with minimal off-target effects. Our goal was to establish an integrated database using available transcriptome-level datasets and to create a web-platform enabling mining of this database by comparing normal, tumor and metastatic data across all genes in real time.

We utilized data generated by either gene arrays or RNA-seq. Gene array data were manually selected from NCBI-GEO. RNA sequencing data was downloaded from the TCGA, TARGET, and GTEx repositories. TCGA and TARGET contain predominantly tumor and metastatic samples from adult and pediatric patients, while GTEx samples are from healthy tissues. Statistical significance was computed using Mann-Whitney or Kruskall-Wallis tests.

The entire database contains 56,938 samples including 33,520 samples from 3,180 gene chip-based studies (453 metastatic, 29,376 tumorous and 3,691 normal samples), 11,010 samples from TCGA (394 metastatic, 9,886 tumorous and 730 normal), 1,193 samples from TARGET (1 metastatic, 1,180 tumor, 12 normal) and 11,215 normal samples from GTEx. The most consistently up-regulated genes across multiple tumor types were TOP2A (mean FC=7.8), SPP1 (FC=7.0) and CENPA (FC=6.03) and the most consistently down-regulated gene was ADH1B (mean FC=0.15). Validation of differential expression using equally sized training and test sets confirmed reliability of the database in breast, colon, and lung cancer (p<0.0001). The online analysis platform enables unrestricted mining of the database and is accessible atwww.tnmplot.com.
driveR: A Novel Method for Prioritizing Cancer Driver Genes Using Somatic Genomics Data
Authors: Ülgen Ege , Sezerman O. Uğur
Published: November 2020

Cancer develops due to “driver” alterations. Numerous approaches exist for predicting cancer drivers from cohort-scale genomic data. However, methods for personalized analysis of driver genes are underdeveloped.

In this study, we developed a novel personalized/batch analysis approach for driver gene prioritization utilizing somatic genomic data, called driveR. Combining genomic information and prior biological knowledge, driveR accurately prioritizes cancer driver genes via a multi-task learning model.

Testing on 28 different datasets, this study demonstrates that driveR performs adequately, outperforms existing approaches, and is an accurate and easy-to-utilize approach for prioritizing driver genes in cancer genomes. driveR is available on CRAN:https://cran.r-project.org/package=driveR.
Epigenome-Wide Study of Brain DNA Methylation Among Opioid Users and Controls
Authors: Shu Chang , Sosnowski David W. , Tao Ran , Deep-Soboslay Amy , Kleinman Joel E. , Hyde Thomas M. , Jaffe Andrew E. , Sabunciyan Sarven , Maher Brion S.
Published: November 2020

Opioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. To clarify the association between opioid abuse and DNA methylation, we conducted an epigenome-wide analysis (EWAS) of DNA methylation in brains of individuals who died from opioid intoxication and controls. Tissue samples were extracted from the dorsolateral prefrontal cortex of 160 deceased individuals (Mage= 35.15,SD= 9.42 years; 62% male; 78% White). The samples included 73 individuals who died of opioid intoxication, 59 group-matched psychiatric controls, and 28 group-matched normal controls. EWAS was implemented using the Illumina Infinium MethylationEPIC BeadChip; analyses adjusted for sociodemographic characteristics, negative control and ancestry principal components, cellular composition, and surrogate variables. Epigenetic age was calculated using the Horvath and Levine clocks, and gene ontology (GO) analyses were performed. No CpG sites were epigenome-wide significant after multiple testing correction, but 13 sites reached nominal significance (p < 1.0 x 10-5). There was a significant association between opioid use and Levine phenotypic age (b= 2.24,se= 1.11,p= .045). Opioid users were approximately two years phenotypically older compared to controls. GO analyses revealed enriched pathways related to cell function and neuron differentiation, but no terms survived multiple testing correction. Results inform our understanding of the neurobiology of opioid use, and future research with larger samples across stages of opioid use will elucidate the complex genomics of opioid abuse.
CoaTran: Coalescent tree simulation along a transmission network
Authors: Moshiri Niema
Published: November 2020

Motivation

The ability to simulate coalescent viral phylogenies constrained by a given transmission network can enable the benchmarking of computational tools used in molecular epidemiology as well as the ability to gain insights into unobservable aspects of the virology of a novel pathogen. However, such simulation experiments require generating a large number of technical simulation replicates, and existing tools for coalescent simulations along a transmission network are too slow to conduct such experiments at the scale of the global population.

Results

CoaTran is a massively scalable tool that simulates a coalescent viral phylogeny constrained by a user-provided transmission network. CoaTran is written in highly-optimized C++ code and can generate global population scale phylogenetic coalescent simulations in seconds to minutes.

Availability

CoaTran is freely available athttps://github.com/niemasd/CoaTranas an open-source software project.

Contact

niema@ucsd.edu

Supplementary information

Supplementary data are available online.
Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma
Authors: Prummel Karin D. , Crowell Helena L. , Nieuwenhuize Susan , Brombacher Eline C. , Daetwyler Stephan , Soneson Charlotte , Kresoja-Rakic Jelena , Ronner Manuel , Kocere Agnese , Ernst Alexander , Labbaf Zahra , Clouthier David E. , Firulli Anthony B. , Sánchez-Iranzo Héctor , Naganathan Sundar R. , O’Rourke Rebecca , Raz Erez , Mercader Nadia , Burger Alexa , Felley-Bosco Emanuela , Huisken Jan , Robinson Mark D. , Mosimann Christian
Published: November 2020

The mesothelium forms epithelial membranes that line the bodies cavities and surround the internal organs. Mesothelia widely contribute to organ homeostasis and regeneration, and their dysregulation can result in congenital anomalies of the viscera, ventral wall defects, and mesothelioma tumors. Nonetheless, the embryonic ontogeny and developmental regulation of mesothelium formation has remained uncharted. Here, we combine genetic lineage tracing,in totolive imaging, and single-cell transcriptomics in zebrafish to track mesothelial progenitor origins from the lateral plate mesoderm (LPM). Our single-cell analysis uncovers a post-gastrulation gene expression signature centered onhand2that delineates distinct progenitor populations within the forming LPM. Combining gene expression analysis and imaging of transgenic reporter zebrafish embryos, we chart the origin of mesothelial progenitors to the lateral-most,hand2-expressing LPM and confirm evolutionary conservation in mouse. Our time-lapse imaging of transgenichand2reporter embryos captures zebrafish mesothelium formation, documenting the coordinated cell movements that form pericardium and visceral and parietal peritoneum. We establish that the primordial germ cells migrate associated with the forming mesothelium as ventral migration boundary. Functionally,hand2mutants fail to close the ventral mesothelium due to perturbed migration of mesothelium progenitors. Analyzing mouse and human mesothelioma tumors hypothesized to emerge from transformed mesothelium, we findde novoexpression of LPM-associated transcription factors, and in particular of Hand2, indicating the re-initiation of a developmental transcriptional program in mesothelioma. Taken together, our work outlines a genetic and developmental signature of mesothelial origins centered around Hand2, contributing to our understanding of mesothelial pathologies and mesothelioma.
Exposure to Airborne Bacteria Depends upon Vertical Stratification and Vegetation Complexity
Authors: Robinson Jake M. , Cando-Dumancela Christian , Antwis Rachael E. , Cameron Ross , Liddicoat Craig , Poudel Ravin , Weinstein Philip , Breed Martin F.
Published: November 2020

Exposure to biodiverse aerobiomes may support human health, but it is unclear which ecological factors influence exposure. Few studies have investigated near-surface green space aerobiome dynamics, and no studies have investigated aerobiome vertical stratification in different green spaces. We used columnar sampling and next generation sequencing of the bacterial 16S rRNA gene, combined with geospatial and network analyses to investigate aerobiome spatio-compositional dynamics. We show a strong effect of habitat on bacterial diversity and network complexity. We observed aerobiome vertical stratification and network complexity that was contingent on habitat type. Tree density, closer proximity, and canopy coverage associated with greater aerobiome alpha diversity. Grassland aerobiomes exhibited greater proportions of putative pathogens compared to scrub, and also stratified vertically. We provide new insights into the urban ecosystem with potential importance for public health, whereby the possibility of differential aerobiome exposures appears to depend on habitat type and height in the airspace.
Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics
Authors: Gordillo-Marañón María , Zwierzyna Magdalena , Charoen Pimphen , Drenos Fotios , Chopade Sandesh , Shah Tina , Engmann Jorgen , Casas Juan-Pablo , Chaturvedi Nishi , Papacosta Olia , Wannamethee Goya , Wong Andrew , Sofat Reecha , Kivimaki Mika , Price Jackie F , Hughes Alun D , Gaunt Tom R , Lawlor Deborah A , Gaulton Anna , Hingorani Aroon D , Schmidt Amand F , Finan Chris
Published: November 2020

Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter its expression or function, as a tool to anticipate the effect of drug action on the same target. Here, we applied MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets were further prioritized using genetic co-localization, protein expression profiles from the Human Protein Atlas and, for targets with a licensed drug or an agent in clinical development, by sourcing data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with circulating blood lipids (HDL-C, LDL-C and triglycerides), we were able to robustly prioritize 30 targets that might elicit beneficial treatment effects in the prevention or treatment of CHD. The prioritized list included NPC1L1 and PCSK9, the targets of licensed drugs whose efficacy has been already proven in clinical trials. To conclude, we discuss how this approach can be generalized to other targets, disease biomarkers and clinical end-points to help prioritize and validate targets during the drug development process.

One Sentence Summary

We provide genetic support for lipid-modifying drug targets for coronary heart disease prevention using drug target Mendelian randomization and further prioritization based on clinical and biological evidence.
Nonrandom spatial distribution of Neotropic Cormorants (Phalacrocorax brasilianus) along a coastal highway in Lima, Peru
Authors: Lozano-Sanllehi Sebastián , Zavalaga Carlos B.
Published: November 2020

Neotropic Cormorants (Phalacrocorax brasilianus) are common seabirds along the Peruvian coast. They frequently perch on trees, poles and port structures in urban areas, causing discomfort and esthetic problems due to the dropping of their feces on infrastructure and people. Hundreds of these birds rest on lighting poles and telephone cables along a 12.7 km highway in the coastal strip of the city of Lima, Peru. We hypothesized that the distribution of the cormorants along this highway is clustered and could be associated with physical features of both the coast and the adjacent marine area. Half-monthly or monthly surveys were performed from July 2018 to March 2020 in the Circuito de Playas de la Costa Verde highway. At each survey, cormorants were counted per lighting pole and adjacent telephone cables (pole-cable) at four count hours (0600 h, 1000 h, 1400 h and 1800 h). Our results revealed that daily bird numbers varied from 46 to 457 individuals and that only 17% of the total number of pole-cables (N = 651) was occupied once by at least one individual. The number of cormorants also varied between count hours within the same day (higher numbers at 1000 h and 1400 h). Birds were clustered into a maximum of five hotspots along the highway. According to the Akaike’s information-theoretic approach applied to Poisson GLMM, higher numbers of cormorants on pole-cables were associated mainly to a closer distance from these structures to the shoreline and to the surf zone, suggesting that Neotropic Cormorants may select such pole-cables as optimal sites for sighting and receiving clues of prey availability. Based on the results, the use of nonlethal deterrents and the relocation of these birds to other perching structures on nearby groynes could be the most suitable and eco-friendly solution for the problems caused by their droppings.
Default Mode Network Ventral Hub Connectivity Associated with Memory Impairment in Temporal Lobe Epilepsy Surgery
Authors: Neal Elliot G. , Di Long , Park You Jeong , Finch Austin , Korneli Ferdinand , Maciver Stephanie , Bezchlibnyk Yarema B. , Schoenberg Mike R. , Vale Fernando L.
Published: November 2020

In patients undergoing surgery for intractable temporal lobe epilepsy, the relationship between the default mode network and patients’ neurocognitive outcome remains unclear. The objective of this study is to employ non-invasive network mapping to identify the relationship between subdivisions of the default mode network and neurocognitive function before and after epilepsy surgery in patients with temporal lobe epilepsy.

Twenty-seven medically patients with medically refractory temporal lobe epilepsy were prospectively enrolled and received resting state functional MRI and neuropsychological testing both pre- and post-operatively. Connectivity within the default mode network was modeled and average connectivity within the networks was calculated.

Higher pre-operative connectivity in the ventral default mode network hub correlated with impaired baseline performance in a visual memory task. Post-operatively, a decrease in ventral but not dorsal default mode network connectivity was correlated with a deterioration of verbal and logical memory after surgery.

Overall, higher connectivity in the ventral default mode network hub was associated with poor memory function in patients with temporal lobe epilepsy both before and after temporal lobe surgery. Pre-operatively, higher ventral connectivity was associated with worse visual function. Post-operatively, decreased connectivity of the ventral and dorsal default mode network was correlated with a greater decrease in logical and verbal memory when compared with the pre-operation baseline. An imbalance in default mode network connectivity towards the ventral stream and more widespread epilepsy networks may be used to predict memory impairments following surgical intervention and may lead to more tailored surgical decision making based on this non-invasive network modeling.
Detection and functional resolution of soluble multimeric immune complexes by a comprehensive FcγR reporter cell panel
Authors: Chen Haizhang , Maul-Pavicic Andrea , Holzer Martin , Huber Magdalena , Salzer Ulrich , Chevalier Nina , Voll Reinhard E. , Hengel Hartmut , Kolb Philipp
Published: November 2020

Fc-gamma receptor (FcγR) activation by soluble IgG immune complexes (sICs) represents a major mechanism of inflammation in certain autoimmune diseases such as systemic lupus erythematosus (SLE). A robust and scalable test system allowing for the detection and quantification of sIC bioactivity is missing. Previously described FcγR interaction assays are limited to certain FcγRs, lack scalability and flexibility, are not indicative of receptor activation or lack sensitivity towards sIC size. We developed a comprehensive reporter cell panel detecting individual activation of FcγRs from humans and the mouse. The reporter cell lines were integrated into an assay format that provides flexible read-outs enabling the quantification of sIC reactivity via ELISA or a fast detection using flow cytometry. This identified FcγRIIA(H) and FcγRIIIA as the most sIC-sensitive FcγRs in our test system. Applying the assay we demonstrate that sICs versus immobilized ICs are fundamentally different FcγR-ligands with regard to FcγR preference and signal strength. Reaching a detection limit in the very low nanomolar range, the assay proved also to be sensitive to sIC stoichiometry and size enabling for the first time a complete reproduction of the Heidelberger-Kendall precipitation curve in terms of immune receptor activation. Analyzing sera from SLE patients and mouse models of lupus and arthritis proved that sIC-dependent FcγR activation has predictive capabilities regarding severity of SLE disease. The new methodology provides a sensitive, scalable and comprehensive tool to evaluate the size, amount and bioactivity of sICs in all settings.

One Sentence Summary

In this study we established a comprehensive FcγR reporter cell assay enabling the detection and quantification of soluble immune complexes generated in experimental and clinical settings.
Mechanistic Dissection of Spatial Organization in NF-κB Signaling Pathways by Hybrid Simulations
Authors: Wu Yinghao , Dhusia Kalyani , Su Zhaoqian
Published: November 2020

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is one of the most important transcription factors involved in the regulation of inflammatory signaling pathways. Inappropriate activation of these pathways has been linked to autoimmunity and cancers. Emerging experimental evidences have been showing the existence of elaborate spatial organizations for various molecular components in the pathways. One example is the scaffold protein tumor necrosis factor receptor associated factor (TRAF). While most TRAF proteins form trimeric quaternary structure through their coiled-coil regions, the N-terminal region of some members in the family can further be dimerized. This dimerization of TRAF trimers can drive them into higher-order clusters as a response to receptor stimulation, which functions as a spatial platform to mediate the downstream poly-ubiquitination. However, the molecular mechanism underlying the TRAF protein clustering and its functional impacts are not well-understood. In this article, we developed a hybrid simulation method to tackle this problem. The assembly of TRAF-based signaling platform at the membrane-proximal region is modeled with spatial resolution, while the dynamics of downstream signaling network, including the negative feedbacks through various signaling inhibitors, is simulated as stochastic chemical reactions. These two algorithms are further synchronized under a multiscale simulation framework. Using this computational model, we illustrated that the formation of TRAF signaling platform can trigger an oscillatory NF-κB response. We further demonstrated that the temporal patterns of downstream signal oscillations are closely regulated by the spatial factors of TRAF clustering, such as the geometry and energy of dimerization between TRAF trimers. In general, our study sheds light on the basic mechanism of NF-κB signaling pathway and highlights the functional importance of spatial regulation within the pathway. The simulation framework also showcases its potential of application to other signaling pathways in cells.
A cloud platform for atomic pair distribution function analysis: PDFitc
Authors: Yang Long , Culbertson Elizabeth A. , Thomas Nancy K. , Vuong Hung T. , Kjær Emil T. S. , Jensen Kirsten M. Ø. , Tucker Matthew G. , Billinge Simon J. L.
Published: November 2020

A cloud web platform for analysis and interpretation of atomic pair distribution function (PDF) data (PDFitc) is described. The platform is able to host applications for PDF analysis to help researchers study the local and nanoscale structure of nanostructured materials. The applications are designed to be powerful and easy to use and can, and will, be extended over time through community adoption and development. The currently available PDF analysis applications, structureMining, spacegroupMining and similarityMapping, are described. In the first and second the user uploads a single PDF and the application returns a list of best-fit candidate structures, and the most likely space group of the underlying structure, respectively. In the third, the user can upload a set of measured or calculated PDFs and the application returns a matrix of Pearson correlations, allowing assessment of the similarity between different data sets. structureMining is presented here as an example to show the easy-to-use workflow on PDFitc. In the future, as well as using the PDFitc applications for data analysis, it is hoped that the community will contribute their own codes and software to the platform.