bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular rotary motors: Unidirectional motion around double bonds
Authors: Roke Diederik , Wezenberg Sander J. , Feringa Ben L.
Published: April 2018

The field of synthetic molecular machines has quickly evolved in recent years, growing from a fundamental curiosity to a highly active field of chemistry. Many different applications are being explored in areas such as catalysis, self-assembled and nanostructured materials, and molecular electronics. Rotary molecular motors hold great promise for achieving dynamic control of molecular functions as well as for powering nanoscale devices. However, for these motors to reach their full potential, many challenges still need to be addressed. In this paper we focus on the design principles of rotary motors featuring a double-bond axle and discuss the major challenges that are ahead of us. Although great progress has been made, further design improvements, for example in terms of efficiency, energy input, and environmental adaptability, will be crucial to fully exploit the opportunities that these rotary motors offer.
FACT complex is required for DNA demethylation at heterochromatin during reproduction in
Arabidopsis
Authors: Frost Jennifer M. , Kim M. Yvonne , Park Guen Tae , Hsieh Ping-Hung , Nakamura Miyuki , Lin Samuel J. H. , Yoo Hyunjin , Choi Jaemyung , Ikeda Yoko , Kinoshita Tetsu , Choi Yeonhee , Zilberman Daniel , Fischer Robert L.
Published: April 2018

Significance

The chromatin remodeling activities of the FACT (facilitates chromatin transactions) complex are required for many cellular functions, including transcription, DNA replication, and repair. Here, we demonstrate that the two FACT subunits, SSRP1 and SPT16, are also required for genome-wide DNA demethylation and regulation of gene imprinting during
Arabidopsis
reproduction. Without FACT,
Arabidopsis
seeds undergo abnormal development and exhibit aberrant DNA hypermethylation, including at imprinting control region loci. We show that FACT associates with the DEMETER (DME) DNA demethylase, facilitating DNA demethylation at over half of DME’s targets, specifically those which reside in heterochromatin. These results provide insight into upstream events in the DNA demethylation pathway and reveal the importance of chromatin remodeling for DNA demethylation during
Arabidopsis
reproduction.
Systematic analysis of copy number variation associated with congenital diaphragmatic hernia
Authors: Zhu Qihui , High Frances A. , Zhang Chengsheng , Cerveira Eliza , Russell Meaghan K. , Longoni Mauro , Joy Maliackal P. , Ryan Mallory , Mil-homens Adam , Bellfy Lauren , Coletti Caroline M. , Bhayani Pooja , Hila Regis , Wilson Jay M. , Donahoe Patricia K. , Lee Charles
Published: April 2018

Significance

This study describes the results of a large-scale case control analysis of copy number variants (CNVs) in a cohort of patients with congenital diaphragmatic hernia (CDH) and a large number of healthy population-matched controls. Using a customized array comparative genomic hybridization system, we have identified six CNVs that are associated with CDH with statistical significance (P< 0.05). These regions validate several hypothesized CDH candidate genes and identify additional genes and pathways that contribute to the pathogenesis of CDH. The estimated frequency of pathogenic CNVs in this cohort is 13%, which underscores the critical contribution of CNVs in CDH. This study also provides a model approach that is broadly applicable to other structural birth defects and identifies candidates for future functional studies.
Distinct gating mechanism of SOC channel involving STIM–Orai coupling and an intramolecular interaction of Orai in
Caenorhabditis elegans
Authors: Kim Kyu Min , Wijerathne Tharaka , Hur Jin-Hoe , Kang Uk Jung , Kim Ihn Hyeong , Kweon Yeong Cheon , Lee Ah Reum , Jeong Su Ji , Lee Sang Kwon , Lee Yoon Young , Sim Bo-Woong , Lee Jong-Hee , Baig Chunggi , Kim Sun-Uk , Chang Kyu-Tae , Lee Kyu Pil , Park Chan Young
Published: April 2018

Significance

Store-operated calcium entry (SOCE) is a widespread, essential signaling mechanism for cellular functions in both invertebrates and vertebrates and is controlled by two membrane proteins, STIM in the endoplasmic reticulum (ER) and Orai, in the plasma membrane (PM). How these proteins residing in two different compartments have evolved to interact with each other has not been elucidated. We show that
Caenorhabditis elegans
has a distinct mechanism of SOCE in which the 2–3 loop is regulated by STIM1 and the N and C termini of Orai1 by intramolecular interaction, differing from the previously reported mechanism of human SOCE. Therefore our studies suggest that, while the STIM–Orai interaction has been conserved from invertebrates to mammals, the gating mechanism for Orai has evolved considerably.
Quantifying flow and stress in ice mélange, the world’s largest granular material
Authors: Burton Justin C. , Amundson Jason M. , Cassotto Ryan , Kuo Chin-Chang , Dennin Michael
Published: April 2018

Significance

Ice mélange, a granular collection of broken icebergs ranging from tens of meters to hundreds of meters in size, sits in front of many of the Earth’s most active tidewater glaciers. In addition to influencing heat and mass transport in the ocean, the jam-packed mélange provides a geophysical living laboratory to test principles developed for small-scale granular materials such as sand. By characterizing both flow and mechanical stress using field measurements, laboratory experiments, and numerical modeling, we show that ice mélange is a quasi-2D, creeping granular fluid which constantly jams and unjams as it advances through the fjord. Most importantly, our results show how ice mélange can act as a “granular ice shelf” which buttresses even the largest icebergs that calve into the ocean.
The C-terminal extension landscape of naturally presented HLA-I ligands
Authors: Guillaume Philippe , Picaud Sarah , Baumgaertner Petra , Montandon Nicole , Schmidt Julien , Speiser Daniel E. , Coukos George , Bassani-Sternberg Michal , Filippakopoulos Panagis , Gfeller David
Published: April 2018

Significance

HLA-I molecules play a central role in immune recognition of infected or cancer cells. They bind short intracellular peptides of 9 to 12 amino acids and present them to T cells for immune recognition. For many years, the confinement of HLA-I ligand has been a central dogma in immunology. Combing analysis of mass spectrometry data with novel algorithms, X-ray crystallography, and T cell recognition assays, we show that a substantial fraction of HLA-I molecules bind peptides extending beyond the C terminus of canonical ligands, and that these peptides can be recognized by CD8 T cells. Our ability to accurately predict such epitopes will help studying their role in infectious diseases or cancer immunotherapy.
Symbiotic polydnavirus and venom reveal parasitoid to its hyperparasitoids
Authors: Zhu Feng , Cusumano Antonino , Bloem Janneke , Weldegergis Berhane T. , Villela Alexandre , Fatouros Nina E. , van Loon Joop J. A. , Dicke Marcel , Harvey Jeffrey A. , Vogel Heiko , Poelman Erik H.
Published: April 2018

Significance

Symbiotic relationships benefit organisms in utilization of new niches. In parasitoid wasps, symbiotic viruses and venom that are injected together with wasp eggs into the host caterpillar suppress immune responses of the host and enhance parasitoid survival. We found that the virus also has negative effects on offspring survival when placing these interactions in a community context. The virus and venom drive a chain of interactions that includes the herbivore and its food plant and attracts the hyperparasitoid enemies of the parasitoid. Our results shed new light on the importance of symbionts associated with their host in driving ecological interactions and highlight the intricacy of how multispecies interactions are reflected in adaptations of individual species such as the host-finding behavior of hyperparasitoids.
Quantum indistinguishability in chemical reactions
Authors: Fisher Matthew P. A. , Radzihovsky Leo
Published: April 2018

Significance

Counter to conventional approaches that treat nuclear coordinates classically, we explore quantum indistinguishability of nuclei in enzymatic chemical reactions of small symmetric molecules. Supported by several physical arguments, we conjecture a far-reaching “quantum dynamical selection” (QDS) rule that precludes enzymatic chemical bond-breaking reactions from orbitally nonsymmetric molecular states. We propose and discuss experimental implications of QDS, such as (
i
) differential chemical reactivity in ortho- and parahydrogen, (
ii
) a mass-independent mechanism for isotope fractionation, (
iii
) an explanation of the enhanced chemical activity of “reactive oxygen species”, (
iv
) a route to parahydrogen-induced hyperpolarization important for zero-field NMR spectroscopy, and (
v
) critical quantum-to-biochemical linkage in the nuclear spin model of the (putative) quantum brain, among others.
Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy
Authors: Liao Xudong , Shen Yuyan , Zhang Rongli , Sugi Keiki , Vasudevan Neelakantan T. , Alaiti M. Amer , Sweet David R. , Zhou Lin , Qing Yulan , Gerson Stanton L. , Fu Chen , Wynshaw-Boris Anthony , Hu Rui , Schwartz Martin A. , Fujioka Hisashi , Richardson Brian , Cameron Mark J. , Hayashi Hiroki , Stamler Jonathan S. , Jain Mukesh K.
Published: April 2018

Significance

Pressure overload triggers responses in cardiomyocytes and noncardiomyocytes, leading to pressure overload hypertrophy (POH). Here, we show that cardiac resident macrophages regulate compensatory myocardial adaptation to POH, while nonresident infiltrating macrophages are detrimental. At early-phase POH, pressure overload induces cardiac resident macrophage proliferation, which is regulated by Kruppel-like factor 4. At late-phase POH, pressure overload also induces Ly6C
hi
monocyte infiltration, and its blockade improves myocardial angiogenesis and preserves cardiac function. Mechanistically, the differential impact of these two macrophage subsets on myocardial angiogenesis may underlie the cardiac phenotype. These findings provide insights regarding the role of cardiac resident and nonresident macrophages, conceptually update the view of myocardial angiogenesis, and identify monocyte infiltration as a therapeutic target for nonischemic cardiomyopathy.
Genomic adaptation to drought in wild barley is driven by edaphic natural selection at the Tabigha Evolution Slope
Authors: Wang Xiaolei , Chen Zhong-Hua , Yang Chongyi , Zhang Xuelei , Jin Gulei , Chen Guang , Wang Yuanyuan , Holford Paul , Nevo Eviatar , Zhang Guoping , Dai Fei
Published: April 2018

Significance

Microsite evolution involving ecological divergence due to geological, edaphic, or climatic conditions requires adaptive complexes to environmental stresses. The higher drought tolerance of wild barley populations inhabiting Terra Rossa soil at the Tabigha Evolution Slope has been described, but the underlying genetic mechanisms remain unknown. Using genome resequencing and RNA-sequencing technologies of wild barley genotypes from contrasting Terra Rossa and basalt soil types, we identified genes in selection sweep regions on chromosomes 6H and 7H, showing divergence in the barley populations from Terra Rossa and basalt soils with significant roles in plant drought tolerance. Our results set a solid foundation for future work on gene discovery and on drought adaptation mechanisms in barley related to the rhizosphere environment.
Symbiotic root infections in
Medicago truncatula
require remorin-mediated receptor stabilization in membrane nanodomains
Authors: Liang Pengbo , Stratil Thomas F. , Popp Claudia , Marín Macarena , Folgmann Jessica , Mysore Kirankumar S. , Wen Jiangqi , Ott Thomas
Published: April 2018

Significance

Pattern recognition receptors control the cellular entry of pathogenic as well as symbiotic microbes. While ligand-induced changes in receptor mobility at the plasma membrane and their localization in membrane nanodomains are general features, the molecular mechanism and the biological relevance of this phenomenon have remained unknown. Here we show that immobilization of the symbiotic cell entry receptor LYK3 in nanodomains requires the presence of actin and two molecular scaffold proteins, FLOT4 and SYMREM1. While FLOT4 forms the initial core structure, infection-induced expression and subsequent physical interaction of SYMREM1 with LYK3 stabilize the activated receptors in membrane nanodomains. This recruitment prevents stimulus-dependent endocytosis and ensures progression of the primary infection thread into root cortical cells.
Butane dihedral angle dynamics in water is dominated by internal friction
Authors: Daldrop Jan O. , Kappler Julian , Brünig Florian N. , Netz Roland R.
Published: April 2018

Significance

The interpretation of rates of reactions that take place in a solvent is complicated because of the entanglement of free-energy and history-dependent friction effects. In this context, the dihedral dynamics of butane has played a paradigmatic role since it is simple yet relevant for conformational transitions in polymers and proteins. We directly extract the friction that governs the dihedral dynamics in butane from simulations. We show that ∼89% of the total friction cannot be described as solvent friction and is caused by degrees of freedom that are orthogonal to the dihedral reaction coordinate. This shows that the hydrodynamic estimate of friction severely fails, even in the simplest molecular reaction.
Mechanistic studies of a small-molecule modulator of SMN2 splicing
Authors: Wang Jingxin , Schultz Peter G. , Johnson Kristen A.
Published: April 2018

Significance

The development of small-molecule therapeutics that act by targeting defined DNA or RNA sequences associated with human disease remains a challenge. RG-7916, a small-molecule drug candidate for the treatment of spinal muscular atrophy (SMA), selectively regulates the alternative splicing (AS) of the
SMN2
gene. Herein, we show that SMN-C2 and -C3, close analogs of RG-7916, act by binding SMN2 pre-mRNA and thereby increasing the affinity of the RNA binding proteins far upstream element binding protein 1 (FUBP1) and KH-type splicing regulatory protein (KHSRP) to the SMN2 pre-mRNA complex. These results suggest that nucleic acid targeted small molecules may have untapped potential for modulating disease processes at the level of pre-mRNA splicing.
An endogenous dAMP ligand inBacillus subtilisclass Ib RNR promotes assembly of a noncanonical dimer for regulation by dATP
Authors: Parker Mackenzie J. , Maggiolo Ailiena O. , Thomas William C. , Kim Albert , Meisburger Steve P. , Ando Nozomi , Boal Amie K. , Stubbe JoAnne
Published: April 2018

Significance

Negative feedback regulation of ribonucleotide reductase (RNR) activity by dATP is important for maintaining balanced intracellular 2ʹ-deoxynucleoside triphosphate (dNTP) pools essential for the high fidelity of DNA replication and repair. To date, this type of allostery has been nearly universally associated with dATP binding to the N-terminal ATP-cone domain of the class Ia RNR large subunit (canonical α2), resulting in an altered quaternary structure that is unable to productively bind the second subunit (β2). Here, we report our studies on activity inhibition by dATP of theBacillus subtilisclass Ib RNR, which lacks a traditional ATP-cone domain. This unprecedented allostery involves deoxyadenosine 5′-monophosphate (dAMP) binding to a newly identified site in a partial N-terminal cone domain, forming an unprecedented noncanonical α2.
Comparative terrestrial feed and land use of an aquaculture-dominant world
Authors: Froehlich Halley E. , Runge Claire A. , Gentry Rebecca R. , Gaines Steven D. , Halpern Benjamin S.
Published: April 2018

Significance

Studies are revealing the potential benefits of shifting human diets away from meat and toward other protein sources, including seafood. The majority of seafood is now, and for the foreseeable future, farmed (i.e., aquaculture). As the fastest-growing food sector, fed aquaculture species increasingly rely on terrestrial-sourced feed crops, but the comparative impact of aquaculture versus livestock on associated feed and land use is unclear––especially if human diets shift. Based on global production data, feed use trends, and human consumption patterns, we simulate how feed-crop and land use may increase by midcentury, but demonstrate that millions of tonnes of crops and hectares could be spared for most, but not all, countries worldwide in an aquaculture-dominant future.
Mechanism for survival of homozygous nonsense mutations in the tumor suppressor gene
BRCA1
Authors: Seo Aaron , Steinberg-Shemer Orna , Unal Sule , Casadei Silvia , Walsh Tom , Gumruk Fatma , Shalev Stavit , Shimamura Akiko , Akarsu Nurten Ayse , Tamary Hannah , King Mary-Claire
Published: April 2018

Significance

Many patients with breast and ovarian cancer carry inherited cancer-predisposing mutations in
BRCA1
. However, virtually no patients have two inherited mutations in
BRCA1
because the DNA repair function of
BRCA1
is essential for embryonic development. We discovered that patients with two nonsense mutations from a specific region of
BRCA1
may survive as the result of naturally occurring alternative splicing that yields a short but partially functional BRCA1 protein. These patients are extremely rare, and are characterized by severe chromosomal fragility, congenital anomalies, and predisposition to childhood cancers.
Optimizing the impact of low-efficacy influenza vaccines
Authors: Sah Pratha , Medlock Jan , Fitzpatrick Meagan C. , Singer Burton H. , Galvani Alison P.
Published: April 2018

Significance

The efficacy of the influenza vaccine against the predominant influenza strain appears to be relatively low during this 2017–2018 season. Our analyses demonstrate the substantial effect of even low-efficacy vaccines in averting infections, hospitalizations, and particularly deaths. Our results also demonstrate that the health burden resulting from influenza is more sensitive to changes to vaccination coverage than to changes to vaccine efficacy. We further determined the uptake distribution of the 140 million doses available that would maximize the effectiveness of vaccination. Our results inform current public health policies and underscore the importance of influenza vaccination.
Insulin
promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism
Authors: Jian Xing , Felsenfeld Gary
Published: April 2018

Significance

We show that in a human pancreatic β cell line the human insulin gene promoter on chromosome 11 physically contacts sites on other chromosomes. Many of these contacted sites contain type 1 or type 2 diabetes susceptibility loci. We find that insulin gene expression can affect expression of contacted genes on other chromosomes. Some of these genes, in turn, regulate insulin secretion. These results reveal physical regulatory mechanisms in which the level of insulin expression controls expression of genes involved in insulin transport and metabolism. We study the properties of one such gene, somatostatin receptor 5 antisense (
SSTR5-AS1
), and show that it regulates
SSTR5
expression, which affects insulin secretion. Analysis of insulin contacts thus may reveal new insulin metabolic pathways.
Centrobin is essential for C-tubule assembly and flagellum development in Drosophila melanogaster spermatogenesis
Authors: Reina Jose , Gottardo Marco , Riparbelli Maria G. , Llamazares Salud , Callaini Giuliano , Gonzalez Cayetano
Published: April 2018

Centrobin homologues identified in different species localize on daughter centrioles. In Drosophila melanogaster sensory neurons, Centrobin (referred to as CNB in Drosophila) inhibits basal body function. These data open the question of CNB’s role in spermatocytes, where daughter and mother centrioles become basal bodies. In this study, we report that in these cells, CNB localizes equally to mother and daughter centrioles and is essential for C-tubules to attain the right position and remain attached to B-tubules as well as for centrioles to grow in length. CNB appears to be dispensable for meiosis, but flagellum development is severely compromised in Cnb mutant males. Remarkably, three N-terminal POLO phosphorylation sites that are critical for CNB function in neuroblasts are dispensable for spermatogenesis. Our results underpin the multifunctional nature of CNB that plays different roles in different cell types in Drosophila, and they identify CNB as an essential component for C-tubule assembly and flagellum development in Drosophila spermatogenesis.
Brain Mapping of drug addiction in witdrawal condition based P300 Signals
Authors: Turnip Arjon , Kusumandari Dwi Esti , Hidayat Teddy
Published: April 2018

Drug abuse for a long time will slowly cause changes in brain structure and performance. These changes tend to occur in the front of the brain which is directly interfere the concentration and the decision-making process. In this study an experiment involving 10 drug users was performed. The process of recording data with EEG system is conducted during craving condition and 1 hour after taking methadone. From brain mapping results obtained that brain activity tend to occur in the upper layer of the brain during craving conditions and tend to be in the midle layer of the brain after one hour of taking methadone.
What Could Total Worker Health® Look Like in Small Enterprises?
Authors: Rohlman Diane S , Campo Shelly , Hall Jennifer , Robinson Erin L , Kelly Kevin M
Published: April 2018

Small enterprises have fewer resources, are more financially precarious, and have higher rates of occupational injury and illness compared with larger enterprises. Interventions that address the promotion of health and well-being in addition to traditional occupational safety and health hazards, a Total Worker Health® (TWH) approach, may be effective in reducing injuries and preventing illness. However, little research has examined the impact of TWH interventions in small enterprises. The aim of this research was to explore and characterize health and safety practices, policies, and programs in small Midwestern enterprises from a TWH perspective. Utilizing a case studies approach, site visits were conducted with small business, between 10 and 250 employees, from 2014 through 2016 and included workplace audits and interviews with multiple employees in varying roles within each organization. Both open and closed coding were used to identify specific themes. Eight themes emerged from the site visits: value and return on investment, organizational factors, program design, engaging employees, low-cost strategies, evaluation, and integration. These themes overlapped with both the National Institute for Occupational Safety and Health’s (NIOSH) Essential Elements of TWH and the NIOSH Fundamentals. Industry sector and enterprise size also affect resources and integration of these resources. As TWH expands to organizations of all sizes, it is necessary to address the unique needs of smaller enterprises.
A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiologya
Authors: Miller J Michael , Binnicker Matthew J , Campbell Sheldon , Carroll Karen C , Chapin Kimberle C , Gilligan Peter H , Gonzalez Mark D , Jerris Robert C , Kehl Sue C , Patel Robin , Pritt Bobbi S , Richter Sandra S , Robinson-Dunn Barbara , Schwartzman Joseph D , Snyder James W , Telford Sam , Theel Elitza S , Thomson Richard B , Weinstein Melvin P , Yao Joseph D
Published: April 2018

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.
Does Stereotactic Radiosurgery Have a Role in the Management of Patients Presenting With 4 or More Brain Metastases?
Authors: Soike Michael H , Hughes Ryan T , Farris Michael , McTyre Emory R , Cramer Christina K , Bourland J D , Chan Michael D
Published: April 2018

Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) are effective treatments for management of brain metastases. Prospective trials comparing the 2 modalities in patients with fewer than 4 brain metastases demonstrate that overall survival (OS) is similar. Intracranial failure is more common after SRS, while WBRT is associated with neurocognitive decline. As technology has advanced, fewer technical obstacles remain for treating patients with 4 or more brain metastases with SRS, but level I data supporting its use are lacking.

 Observational prospective studies and retrospective series indicate that in patients with 4 or more brain metastases, performance status, total volume of intracranial disease, histology, and rate of development of new brain metastases predict outcomes more accurately than the number of brain metastases. It may be reasonable to initially offer SRS to some patients with 4 or more brain metastases. Initiating therapy with SRS avoids the acute and late sequelae of WBRT. Multiple phase III trials of SRS vs WBRT, both currently open or under development, are directly comparing quality of life and OS for patients with 4 or more brain metastases to help answer the question of SRS appropriateness for these patients.
Recovery Plan for Monilinia polystroma Causing Asiatic Brown Rot of Stone Fruit
Authors: Cox K. D. , Villani S. M. , Poniatowska Anna , Schnabel Guido , Holb Imre , Fajardo Julius
Published: April 2018

Stone fruit are an economically important group of specialty fruit crops in the United States. Species of the fungal genus Monilinia are some of the most important pathogens of stone fruit worldwide. These pathogens cause blossom blight, shoot blight, and brown fruit rot in temperate production regions. The most common species of Monilinia pathogenic on stone fruit include Monilinia fructicola, M. laxa, M. fructigena, and M. polystroma. Presently, neither M. polystroma, the causal agent of “Asiatic brown rot”, nor M. fructigena, one of the causal agents of “European brown rot”, have been reported in North America. Interestingly, both species can also cause brown rot of apple, which is densely planted in the eastern United States. This recovery plan was produced as part of the National Plant Disease Recovery System (NPDRS), called for in Homeland Security Presidential Directive Number 9 (HSPD-9) to ensure that the tools, infrastructure, communication networks, and capacity required to mitigate the impact of high-consequence plant disease outbreaks are such that a reasonable level of crop production is maintained. It is intended to provide a brief primer on the disease, assess the status of critical recovery components, and identify disease management research, extension, and education needs.
A systems framework for national assessment of climate risks to infrastructure
Authors: Dawson Richard J. , Thompson David , Johns Daniel , Wood Ruth , Darch Geoff , Chapman Lee , Hughes Paul N. , Watson Geoff V. R. , Paulson Kevin , Bell Sarah , Gosling Simon N. , Powrie William , Hall Jim W.
Published: April 2018

Extreme weather causes substantial adverse socio-economic impacts by damaging and disrupting the infrastructure services that underpin modern society. Globally, $2.5tn a year is spent on infrastructure which is typically designed to last decades, over which period projected changes in the climate will modify infrastructure performance. A systems approach has been developed to assess risks across all infrastructure sectors to guide national policy making and adaptation investment. The method analyses diverse evidence of climate risks and adaptation actions, to assess the urgency and extent of adaptation required. Application to the UK shows that despite recent adaptation efforts, risks to infrastructure outweigh opportunities. Flooding is the greatest risk to all infrastructure sectors: even if the Paris Agreement to limit global warming to 2°C is achieved, the number of users reliant on electricity infrastructure at risk of flooding would double, while a 4°C rise could triple UK flood damage. Other risks are significant, for example 5% and 20% of river catchments would be unable to meet water demand with 2°C and 4°C global warming respectively. Increased interdependence between infrastructure systems, especially from energy and information and communication technology (ICT), are amplifying risks, but adaptation action is limited by lack of clear responsibilities. A programme to build national capability is urgently required to improve infrastructure risk assessment.

This article is part of the theme issue ‘Advances in risk assessment for climate change adaptation policy’.
Climate risk index for Italy
Authors: Mysiak Jaroslav , Torresan Silvia , Bosello Francesco , Mistry Malcolm , Amadio Mattia , Marzi Sepehr , Furlan Elisa , Sperotto Anna
Published: April 2018

We describe a climate risk index that has been developed to inform national climate adaptation planning in Italy and that is further elaborated in this paper. The index supports national authorities in designing adaptation policies and plans, guides the initial problem formulation phase, and identifies administrative areas with higher propensity to being adversely affected by climate change. The index combines (i) climate change-amplified hazards; (ii) high-resolution indicators of exposure of chosen economic, social, natural and built- or manufactured capital (MC) assets and (iii) vulnerability, which comprises both present sensitivity to climate-induced hazards and adaptive capacity. We use standardized anomalies of selected extreme climate indices derived from high-resolution regional climate model simulations of the EURO-CORDEX initiative as proxies of climate change-altered weather and climate-related hazards. The exposure and sensitivity assessment is based on indicators of manufactured, natural, social and economic capital assets exposed to and adversely affected by climate-related hazards. The MC refers to material goods or fixed assets which support the production process (e.g. industrial machines and buildings); Natural Capital comprises natural resources and processes (renewable and non-renewable) producing goods and services for well-being; Social Capital (SC) addressed factors at the individual (people's health, knowledge, skills) and collective (institutional) level (e.g. families, communities, organizations and schools); and Economic Capital (EC) includes owned and traded goods and services. The results of the climate risk analysis are used to rank the subnational administrative and statistical units according to the climate risk challenges, and possibly for financial resource allocation for climate adaptation.

This article is part of the theme issue ‘Advances in risk assessment for climate change adaptation policy’.
Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi
Authors: Berná Luisa , Rodriguez Matias , Chiribao María Laura , Parodi-Talice Adriana , Pita Sebastián , Rijo Gastón , Alvarez-Valin Fernando , Robello Carlos
Published: April 2018

Although the genome of Trypanosoma cruzi, the causative agent of Chagas disease, was first made available in 2005, with additional strains reported later, the intrinsic genome complexity of this parasite (the abundance of repetitive sequences and genes organized in tandem) has traditionally hindered high-quality genome assembly and annotation. This also limits diverse types of analyses that require high degrees of precision. Long reads generated by third-generation sequencing technologies are particularly suitable to address the challenges associated with T. cruzi’s genome since they permit direct determination of the full sequence of large clusters of repetitive sequences without collapsing them. This, in turn, not only allows accurate estimation of gene copy numbers but also circumvents assembly fragmentation. Here, we present the analysis of the genome sequences of two T. cruzi clones: the hybrid TCC (TcVI) and the non-hybrid Dm28c (TcI), determined by PacBio Single Molecular Real-Time (SMRT) technology. The improved assemblies herein obtained permitted us to accurately estimate gene copy numbers, abundance and distribution of repetitive sequences (including satellites and retroelements). We found that the genome of T. cruzi is composed of a ‘core compartment’ and a ‘disruptive compartment’ which exhibit opposite GC content and gene composition. Novel tandem and dispersed repetitive sequences were identified, including some located inside coding sequences. Additionally, homologous chromosomes were separately assembled, allowing us to retrieve haplotypes as separate contigs instead of a unique mosaic sequence. Finally, manual annotation of surface multigene families, mucins and trans-sialidases allows now a better overview of these complex groups of genes.
Efficient Merging of Genome Profile Alignments
Authors: Hennig André , Nieselt Kay
Published: April 2018

Motivation

Whole-genome alignment methods show insufficient scalability towards the generation of large-scale whole-genome alignments (WGAs). Profile alignment-based approaches revolutionized the fields of multiple sequence alignment construction methods by significantly reducing computational complexity and runtime. However, WGAs need to consider genomic rearrangements between genomes, which makes the profile-based extension of several whole-genomes challenging. Currently, none of the available methods offer the possibility to align or extend WGA profiles.

Results

Here, we present GPA, an approach that aligns the profiles of WGAs and is capable of producing large-scale WGAs many times faster than conventional methods. Our concept relies on already available whole-genome aligners, which are used to compute several smaller sets of aligned genomes that are combined to a full WGA with a divide and conquer approach. To align or extend WGA profiles, we make use of the SuperGenome data structure, which features a bidirectional mapping between individual sequence and alignment coordinates. This data structure is used to efficiently transfer different coordinate systems into a common one based on the principles of profiles alignments. The approach allows the computation of a WGA where alignments are subsequently merged along a guide tree. The current implementation uses progressiveMauve (Darling et al., 2010) and offers the possibility for parallel computation of independent genome alignments. Our results based on various bacterial data sets up to several hundred genomes show that we can reduce the runtime from months to hours with a quality that is negligibly worse than the WGA computed with the conventional progressiveMauve tool.

Availability

GPA is freely available at https://lambda.informatik.uni-tuebingen.de/gitlab/ahennig/GPA. GPA is implemented in Java, uses progressiveMauve and offers a parallel computation of WGAs.

Contact

andre.hennig@uni-tuebingen.de
High impact journals in ecology cover proportionally more statistically significant findings
Authors: Ceausu Silvia , Borda-de-Água Luís , Merckx Thomas , Sossai Esther , Sapage Manuel , Miranda Murilo , Pereira Henrique M.
Published: April 2018

Unbiased scientific reporting is crucial for data and research synthesis. Previous studies suggest that statistically significant results are more likely to be published and more likely to be submitted to high impact journals. However, the most recent research on statistical significance in relation to journal impact factors in ecological research was published more than two decades ago or addressed a small subset of the literature. Here, we extract p-values from all articles published in 11 journals in 2012 and 2014 across a wide range of impact factors with six journals sampled in both years. Our results indicate that the proportion of statistically significant results increases with rising impact factor. Such a trend can have important consequences for syntheses of ecological data and it highlights the importance of covering a wide range of impact factors when identifying published studies for data syntheses. This trend can also lead to a biased understanding of the probability of true effects in ecology and conservation. We caution against the possible downplaying of non-significant results by either journals or authors.
Silencing of the CSNK2β gene by siRNA inhibits invasiveness and growth of MDA-MB-231 cells
Authors: Karna Shibendra Kumar Lal , Lone Bilal Ahmad , Ahmad Faiz , Shahi Nerina , Pokharel Yuba Raj
Published: April 2018

Background

Breast cancer is most common cancer and accounts for one-fourth of all cancer diagnoses worldwide. Treatment of triple-negative breast cancer is major challenge and identification of specific drivers is required for targeted therapies. The aim of our present study is to elucidate the therapeutic potential of CSNK2ß silencing in triple negative breast cancer MDA-MB-231 cell.

Methods

CSNK2ß gene has been knockdown using siRNA and silencing was estimated by both real time and western blot. Cell Titer-Glo (CTG) and colony formation assay and wound healing assay, cell cycle analysis by flow cytometry was performed to assess the role of CSNK2ß in cell proliferation, migration, cell cycle, and oncogenesis. Morphological assessment of nuclear condensation, apoptosis by Hoechst staining and measurement of intracellular ROS production was examined using fluorescence microscopy. Real time PCR and western blot was done to study the expression of genes related to cell proliferation, survival, metastasis, apoptosis, and autophagy.

Results

Silencing of CSNK2ß in MDA-MB-231 cells resulted in decreased cell viability, colony formation, and migratory potential. Cell cycle analysis showed that growth inhibitory effect was mediated by arresting the cells in G2/M phase. Furthermore, we demonstrated that silencing of CSNK2ß increased the nuclear condensation and intracellular ROS production. CSNK2ß regulates the expression of BAX, Bcl-xL, caspase 3, Beclin-1, LC3-I, p-ERK, p38-α, c-Myc, MAPK, c-Jun, NF-ĸB, β-catenin, E2F1, PCNA. We have also shown the functional relationship between CSNK2ß, PIN1, and PTOV1 by western blotting. We have first time reported that silencing CSNK2ß using siRNA can inhibit invasiveness and proliferation of MDA-MB-213 cells.

Conclusion

Our results suggested that CSNK2ß silencing may offer future therapeutic target in triple negative breast cancer.
Quantifying protein oligomerization in living cells: A systematic comparison of fluorescent proteins
Authors: Dunsing Valentin , Luckner Madlen , Zühlke Boris , Petazzi Roberto , Herrmann Andreas , Chiantia Salvatore
Published: April 2018

Fluorescence fluctuation spectroscopy has become a popular toolbox for non-disruptive studies of molecular interactions and dynamics in living cells. The quantification of e.g. protein oligomerization and absolute concentrations in the native cellular environment is highly relevant for a detailed understanding of complex signaling pathways and biochemical reaction networks. A parameter of particular relevance in this context is the molecular brightness, which serves as a direct measure of oligomerization and can be easily extracted from temporal or spatial fluorescence fluctuations. However, fluorescent proteins (FPs) typically used in such studies suffer from complex photophysical transitions and limited maturation, potentially inducing non-fluorescent states, which strongly affect molecular brightness measurements. Although these processes have been occasionally reported, a comprehensive study addressing this issue is missing.

Here, we investigate the suitability of commonly used FPs (i.e. mEGFP, mEYFP and mCherry), as well as novel red FPs (i.e. mCherry2, mRuby3, mCardinal, mScarlet and mScarlet-I) for the quantification of oligomerization based on the molecular brightness, as obtained by Fluorescence Correlation Spectroscopy (FCS) and Number&Brightness (N&B) measurements in living cells. For all FPs, we measured a lower than expected brightness of FP homo-dimers, allowing us to estimate, for each fluorescent label, the probability of fluorescence emission in a simple two-state model. By analyzing higher FP homo-oligomers and the Influenza A virus Hemagglutinin (HA) protein, we show that the oligomeric state of protein complexes can only be accurately quantified if this probability is taken into account. Further, we provide strong evidence that mCherry2, an mCherry variant, possesses a superior apparent fluorescence probability, presumably due to its fast maturation. We finally conclude that this property leads to an improved quantification in fluorescence cross-correlation spectroscopy measurements and propose to use mEGFP and mCherry2 as the novel standard pair for studying biomolecular hetero-interactions.
Annual changes in the Biodiversity Intactness Index in tropical and subtropical forest biomes, 2001-2012
Authors: Palma Adriana De , Hoskins Andrew , Gonzalez Ricardo E. , Börger Luca , Newbold Tim , Sanchez-Ortiz Katia , Ferrier Simon , Purvis Andy
Published: April 2018

Few biodiversity indicators are available that reflect the state of broad-sense biodiversity—rather than of particular taxa—at fine spatial and temporal resolution. The Biodiversity Intactness Index (BII) estimates how the average abundance of native terrestrial species in a region compares with their abundances before pronounced human impacts. BII is designed for use with data from a wide range of taxa and functional groups and for estimation at any resolution for which data on land use and related pressures are available. For each year from 2001 to 2012, we combined models of how land use and related pressures in tropical and subtropical forested biomes affect overall abundance and compositional similarity of plants, fungi, invertebrates and vertebrates, with data on anthropogenic pressures to produce annual maps of modelled BII at a spatial resolution of 30 arc seconds (roughly 1 km at the equator) across tropical and subtropical forested biomes. This is the first time temporal change in BII has been estimated across such a large region. The approach we have used to model compositional similarity uses data more efficiently than that used previously when estimating BII. Across tropical and subtropical biomes, BII fell by an average of 1.9 percentage points between 2001 and 2012, with 81 countries seeing an average reduction and 43 an average increase; the extent of primary forest fell by 3.9% over the same period. Changes are not strongly related to countries’ rates of economic growth over the same period.
FORGe: prioritizing variants for graph genomes
Authors: Pritt Jacob , Chen Nae-Chyun , Langmead Ben
Published: April 2018

There is growing interest in using genetic variants to augment the reference genome into a “graph genome” to improve read alignment accuracy and reduce allelic bias. While adding a variant has the positive effect of removing an undesirable alignment-score penalty, it also increases both the ambiguity of the reference genome and the cost of storing and querying the genome index. We introduce methods and a software tool called FORGe for modeling these effects and prioritizing variants accordingly. We show that FORGe enables a range of advantageous and measurable trade-offs between accuracy and computational overhead.
Birth, evolution, and transmission of satellite-free mammalian centromeric domains
Authors: Nergadze Solomon G. , Piras Francesca M. , Gamba Riccardo , Corbo Marco , Cerutti Federico , McCarter Joseph G.W. , Cappelletti Eleonora , Gozzo Francesco , Harman Rebecca M. , Antczak Douglas F. , Miller Donald , Scharfe Maren , Pavesi Giulio , Raimondi Elena , Sullivan Kevin F. , Giulotto Elena
Published: April 2018

Mammalian centromeres are associated with highly repetitive DNA (satellite DNA), which has so far hindered molecular analysis of this chromatin domain. Centromeres are epigenetically specified, and binding of the CENPA protein is their main determinant. In previous work, we described the first example of a natural satellite-free centromere on Equus caballus Chromosome 11. Here, we investigated the satellite-free centromeres of Equus asinus by using ChIP-seq with anti-CENPA antibodies. We identified an extraordinarily high number of centromeres lacking satellite DNA (16 of 31). All of them lay in LINE- and AT-rich regions. A subset of these centromeres is associated with DNA amplification. The location of CENPA binding domains can vary in different individuals, giving rise to epialleles. The analysis of epiallele transmission in hybrids (three mules and one hinny) showed that centromeric domains are inherited as Mendelian traits, but their position can slide in one generation. Conversely, centromere location is stable during mitotic propagation of cultured cells. Our results demonstrate that the presence of more than half of centromeres void of satellite DNA is compatible with genome stability and species survival. The presence of amplified DNA at some centromeres suggests that these arrays may represent an intermediate stage toward satellite DNA formation during evolution. The fact that CENPA binding domains can move within relatively restricted regions (a few hundred kilobases) suggests that the centromeric function is physically limited by epigenetic boundaries.