bluuebunny/crossref_metadata_2025 huggingface dataset:
Vibrational coherence transfer in the ultrafast intersystem crossing of a diplatinum complex in solution
Authors: Monni Roberto , Capano Gloria , Auböck Gerald , Gray Harry B. , Vlček Antonín , Tavernelli Ivano , Chergui Majed
Published: June 2018

Significance

The observation of vibrational wave packets allows tracking the pathways of energy relaxation in nonadiabatic surface crossing events of (bio)molecular systems, such as conical intersections or charge transfer processes. Here, we identify transfer of vibrational coherence in the course of conversion between electronic excited states of different spin in a diplatinum complex in solution, as an example. Retention of coherence is due to the fact that the conversion rate is dramatically accelerated in an acetonitrile solvent due to the strong solvation of higher-lying electronic states that then provide the channel for the coherent population flow from the singlet to the triplet state. These results highlight the role of the environment in controlling the pathways of energy flow and conversion.
Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans
Authors: Værøy Henning , Adori Csaba , Legrand Romain , Lucas Nicolas , Breton Jonathan , Cottard Caroline , do Rego Jean-Claude , Duparc Céline , Louiset Estelle , Lefebvre Hervé , Déchelotte Pierre , Western Elin , Andersson Stein , Hökfelt Tomas , Fetissov Sergueï O.
Published: June 2018

Significance

The number of inmates imprisoned for violent aggression is increasing, as are the penitentiaries, but still our understanding of mechanisms underlying criminality is limited. Our analysis of violent aggressor inmates reveals unique properties of IgG reactive with adrenocorticotropic hormone (ACTH). We show that these IgGs can regulate ACTH-induced cortisol secretion in the adrenal gland, and they exhibit a clear-cut difference in ACTH epitope binding in violent aggressors vs. controls. Additionally, IgG from a subset of aggressive subjects selectively bind to hypothalamic vasopressin neurons. Thus, using several in vitro and in vivo approaches, the study reveals a molecular mechanism involved in the variability of stress response relevant to the neurobiology of aggression and possibly other stress-related conditions.
Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils
Authors: Ruggeri Francesco Simone , Benedetti Fabrizio , Knowles Tuomas P. J. , Lashuel Hilal A. , Sekatskii Sergey , Dietler Giovanni
Published: June 2018

Significance

Today, more than 40 million people worldwide are affected by neurodegenerative disorders. These diseases are associated at the molecular level with the aggregation of specific proteins into insoluble fibrils, termed amyloids. Increasing evidence suggests that the intermediate aggregates, rather than the final fibrillar products, are implicated in toxicity in vivo. However, the investigation of the conversion of proteins into amyloids represents a formidable experimental challenge because of their nanoscale and heterogeneous nature. Here, we report the identification of a mechanism of early assembly of monomeric proteins into elongated intermediates during amyloid formation. The biophysical characterization of novel intermediate molecular species is fundamental to unravel their mechanism of formation and gain insights into their potential toxicity and role in pathology.
Changes in brain architecture are consistent with altered fear processing in domestic rabbits
Authors: Brusini Irene , Carneiro Miguel , Wang Chunliang , Rubin Carl-Johan , Ring Henrik , Afonso Sandra , Blanco-Aguiar José A. , Ferrand Nuno , Rafati Nima , Villafuerte Rafael , Smedby Örjan , Damberg Peter , Hallböök Finn , Fredrikson Mats , Andersson Leif
Published: June 2018

Significance

A common feature of all domestic animals is their tame behavior and lack of fear for humans. Consistent with this, we have previously demonstrated that genes with a role in brain or neural development have been particularly targeted during rabbit domestication. Here we show, using high-resolution magnetic resonance imaging, that domestic rabbits have an altered brain architecture consistent with reduced emotional processing, including attention to behaviorally relevant stimulation, such as fear detection, learning, expression, and control, as well as compromised information processing. The results, here based on rabbits, are significant for understanding both domestication-induced reorganization of brain architecture and how adaptions in brain territories and networks supporting emotion, cognition, and behavior coincide with an altered behavioral repertoire.
Real-time dynamics of mutagenesis reveal the chronology of DNA repair and damage tolerance responses in single cells
Authors: Uphoff Stephan
Published: June 2018

Significance

A central goal in genetics is to understand how mutation rates are regulated by the genome maintenance system in response to DNA damage or drug treatments. This has been challenging because existing mutation assays only show time and population averages of mutation rates and do not resolve the underlying molecular processes. Toward this goal, I utilized a microscopy-based method which enables relating the creation of DNA mismatches to single-cell gene expression dynamics in real time. I show that DNA alkylation damage causes a distinct pulse of mutagenesis that is shaped by the chronology of constitutive and inducible DNA repair and damage tolerance pathways. Stochastic fluctuations in the expression of these pathways modulated the dynamics of mutagenesis in single
Escherichia coli
cells.
Disease outbreak thresholds emerge from interactions between movement behavior, landscape structure, and epidemiology
Authors: White Lauren A. , Forester James D. , Craft Meggan E.
Published: June 2018

Significance

Understanding how emerging infectious and zoonotic diseases spread through space and time is critical for predicting outbreaks and designing interventions; disease models are important tools for realizing these goals. Currently, humans are altering the environment in unprecedented ways through urbanization, habitat fragmentation, and climate change. However, the consequences of increasingly heterogeneous landscapes on pathogen transmission and persistence remain unclear. By synthesizing mathematical modeling and movement ecology approaches, we examined how wildlife movement patterns interact with broad-scale landscape structure to affect population-level disease dynamics. We found that habitat fragmentation could counterintuitively promote disease outbreaks but that, for higher wildlife densities and longer infectious periods, small differences in how hosts navigated their environments could dramatically alter observed disease dynamics.
O
-GlcNAcylation regulates the stability and enzymatic activity of the histone methyltransferase EZH2
Authors: Lo Pei-Wen , Shie Jiun-Jie , Chen Chein-Hung , Wu Chung-Yi , Hsu Tsui-Ling , Wong Chi-Huey
Published: June 2018

Significance

Glycosylation is considered to be a major posttranslational modification, and
O
-GlcNAcylation is known to affect protein folding and function. In this study, we show that the methyltransferase EZH2, which catalyzes the methylation of histone 3 at lysine 27 to form H3K27m3, requires
O
-GlcNAcylation to enhance its stability and enzymatic activity to promote tumor progression. We further show that the
O
-GlcNAcylation in the N-terminal region of EZH2 stabilizes the enzyme and the
O
-GlcNAcylation at S729 in the catalytic domain is essential for its activity of di- and trimethylation. This study indicates that selective inhibition of EZH2
O
-GlcNAcylation may suppress the methylation of H3K27 and thus inhibit tumor progression.
Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease
Authors: Klimtchuk Elena S. , Prokaeva Tatiana , Frame Nicholas M. , Abdullahi Hassan A. , Spencer Brian , Dasari Surendra , Cui Haili , Berk John L. , Kurtin Paul J. , Connors Lawreen H. , Gursky Olga
Published: June 2018

Significance

We identified a one-of-a-kind duplication mutation in human transthyretin (TTR) that causes unusually aggressive systemic amyloidosis. To understand the poor response to treatment with a drug that stabilizes the TTR tetramer, we explored the structure, stability, and drug binding of recombinant proteins. The results suggested that amyloid formation could stem from global destabilization of the monomeric and tetrameric protein as well as the local disordering near the mutation site. This disordering induced proteolysis with release of aggregation-prone fragments. Alternatively, local disordering could trigger misfolding of the full-length protein by exposing an adhesive segment. Drug binding at a dimer interface distant from the mutation site did not significantly influence these pathological processes, indicating the need for alternative therapeutic targets.
Structure of RNA polymerase complex and genome within a dsRNA virus provides insights into the mechanisms of transcription and assembly
Authors: Wang Xurong , Zhang Fuxian , Su Rui , Li Xiaowu , Chen Wenyuan , Chen Qingxiu , Yang Tao , Wang Jiawei , Liu Hongrong , Fang Qin , Cheng Lingpeng
Published: June 2018

Significance

Double-stranded RNA (dsRNA) viruses infect hosts ranging from fungi to plants and to humans. Like most other dsRNA viruses, the aquareovirus RNA polymerase catalyzes the synthesis of RNA plus strands within the inner capsid, a process vital for the replication of virus progeny. Here we present a near-atomic resolution structure of the RNA polymerase in complex with its cofactor protein and genomic RNA within the aquareovirus. Some asymmetric structures within the elaborate viral machine that have never been previously determined have been resolved in our structure, and key interactions among the polymerase, cofactor protein, and dsRNA have been revealed. These findings provide insights into the mechanism underlying highly coordinated dsRNA virus transcription and assembly.
Focal, remote-controlled, chronic chemical modulation of brain microstructures
Authors: Ramadi Khalil B. , Dagdeviren Canan , Spencer Kevin C. , Joe Pauline , Cotler Max , Rousseau Erin , Nunez-Lopez Carlos , Graybiel Ann M. , Langer Robert , Cima Michael J.
Published: June 2018

Significance

The brain is composed of distinct microstructures. Many neurologic and neuropsychiatric diseases arise from dysfunction of circuits of neurons and glia affecting multiple brain regions. Novel potential drug therapies are often delivered through acutely inserted cannulas in the brain. We show that such methods target a much larger region than focal chemical dosing using a class of chronically implanted microprobes. We develop techniques to quantify dynamics of deep-brain infusions and show distinct diffusion behavior of different chemicals. Our microprobes can be independently inserted and combine multiple fluidic lumens in a submillimeter footprint. Studies using implanted drug delivery systems in rodents illustrate our system’s ability to remotely control behavior and the importance of volume in modulating brain regions.
In vivo imaging of the pathophysiological changes and neutrophil dynamics in influenza virus-infected mouse lungs
Authors: Ueki Hiroshi , Wang I-Hsuan , Fukuyama Satoshi , Katsura Hiroaki , da Silva Lopes Tiago Jose , Neumann Gabriele , Kawaoka Yoshihiro
Published: June 2018

Significance

We used a state-of-the-art in vivo imaging system and fluorescent influenza viruses (Color-flu) to determine in real time the pathophysiological changes in the lungs of infected mice. We found that influenza virus infections reduced blood flow speed and decreased neutrophil motility. More significantly, infection with a prototypic “bird flu” strain, a highly pathogenic H5N1 influenza virus, caused higher pulmonary permeability than did infection with a mouse-adapted human influenza virus. This in vivo imaging system with quantitative analyses allowed us to reveal the progression of the disease at the cellular level and to perform a multiparameter analysis that is not possible by using conventional histopathology.
Fast charging of lithium-ion batteries at all temperatures
Authors: Yang Xiao-Guang , Zhang Guangsheng , Ge Shanhai , Wang Chao-Yang
Published: June 2018

Significance

Range anxiety is a key reason that consumers are reluctant to embrace electric vehicles (EVs). To be truly competitive with gasoline vehicles, EVs should allow drivers to recharge quickly anywhere in any weather, like refueling gasoline cars. However, none of today’s EVs allow fast charging in cold or even cool temperatures due to the risk of lithium plating, the formation of metallic lithium that drastically reduces battery life and even results in safety hazards. Here, we present an approach that enables 15-min fast charging of Li-ion batteries in any temperatures (even at −50 °C) while still preserving remarkable cycle life (4,500 cycles, equivalent to >12 y and >280,000 miles of EV lifetime), thus making EVs truly weather-independent.
Piano training enhances the neural processing of pitch and improves speech perception in Mandarin-speaking children
Authors: Nan Yun , Liu Li , Geiser Eveline , Shu Hua , Gong Chen Chen , Dong Qi , Gabrieli John D. E. , Desimone Robert
Published: June 2018

Significance

Musical training is beneficial to speech processing, but this transfer’s underlying brain mechanisms are unclear. Using pseudorandomized group assignments with 74 4- to 5-year-old Mandarin-speaking children, we showed that, relative to an active control group which underwent reading training and a no-contact control group, piano training uniquely enhanced cortical responses to pitch changes in music and speech (as lexical tones). These neural enhancements further generalized to early literacy skills: Compared with the controls, the piano-training group also improved behaviorally in auditory word discrimination, which was correlated with their enhanced neural sensitivities to musical pitch changes. Piano training thus improves children’s common sound processing, facilitating certain aspects of language development as much as, if not more than, reading instruction.
The Life of the Law in the Islamic Republic of Iran
Authors: Banakar Reza , Ziaee Keyvan
Published: June 2018

Beyond the esoteric deliberations of Islamic jurists and their exegesis of criminal and private law doctrines, Iranian law lives a life of its own. It is a life of routine practices of judges, court clerks, lawyers and clients, each of whom is striving to turn the law to their own advantage. It is also a life of contested legality, a relentless struggle over the right to determine the law in a juridical field which is infused with strife and hostility. These conflicts are reproduced daily as two competing conceptions of law, and their corresponding perceptions of legality clash in pursuit of justice. The Iranian judiciary’s concept of law, its reconstruction of Islamic jurisprudence and methods of dispensing justice, which on the surface are reminiscent of Max Weber’s “qādi-justice,” collide with the legal profession’s formal rational understanding thereof. However, Iranian judges are not Weberian qādis, and the legal profession is not a homogenous group of attorneys driven by a collective commitment to the rule of law. To understand their conflict, we need to explore the mundane workings of the legal system in the context of the transformation of Iranian society and the unresolved disputes over the direction of its modernity.
Drosophila immune cells extravasate from vessels to wounds using Tre1 GPCR and Rho signaling
Authors: Thuma Leila , Carter Deborah , Weavers Helen , Martin Paul
Published: June 2018

Inflammation is pivotal to fight infection, clear debris, and orchestrate repair of injured tissues. Although Drosophila melanogaster have proven invaluable for studying extravascular recruitment of innate immune cells (hemocytes) to wounds, they have been somewhat neglected as viable models to investigate a key rate-limiting component of inflammation—that of immune cell extravasation across vessel walls—due to their open circulation. We have now identified a period during pupal development when wing hearts pulse hemolymph, including circulating hemocytes, through developing wing veins. Wounding near these vessels triggers local immune cell extravasation, enabling live imaging and correlative light-electron microscopy of these events in vivo. We show that RNAi knockdown of immune cell integrin blocks diapedesis, just as in vertebrates, and we uncover a novel role for Rho-like signaling through the GPCR Tre1, a gene previously implicated in the trans-epithelial migration of germ cells. We believe this new Drosophila model complements current murine models and provides new mechanistic insight into immune cell extravasation.
JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia
Authors: Mansour Marc R. , He Shuning , Li Zhaodong , Lobbardi Riadh , Abraham Brian J. , Hug Clemens , Rahman Sunniyat , Leon Theresa E. , Kuang You-Yi , Zimmerman Mark W. , Blonquist Traci , Gjini Evisa , Gutierrez Alejandro , Tang Qin , Garcia-Perez Laura , Pike-Overzet Karin , Anders Lars , Berezovskaya Alla , Zhou Yi , Zon Leonard I. , Neuberg Donna , Fielding Adele K. , Staal Frank J.T. , Langenau David M. , Sanda Takaomi , Young Richard A. , Look A. Thomas
Published: June 2018

A substantial subset of patients with T cell acute lymphoblastic leukemia (T-ALL) develops resistance to steroids and succumbs to their disease. JDP2 encodes a bZIP protein that has been implicated as a T-ALL oncogene from insertional mutagenesis studies in mice, but its role in human T-ALL pathogenesis has remained obscure. Here we show that JDP2 is aberrantly expressed in a subset of T-ALL patients and is associated with poor survival. JDP2 is required for T-ALL cell survival, as its depletion by short hairpin RNA knockdown leads to apoptosis. Mechanistically, JDP2 regulates prosurvival signaling through direct transcriptional regulation of MCL1. Furthermore, JDP2 is one of few oncogenes capable of initiating T-ALL in transgenic zebrafish. Notably, thymocytes from rag2:jdp2 transgenic zebrafish express high levels of mcl1 and demonstrate resistance to steroids in vivo. These studies establish JDP2 as a novel oncogene in high-risk T-ALL and implicate overexpression of MCL1 as a mechanism of steroid resistance in JDP2-overexpressing cells.
Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury
Authors: Norris Geoffrey T. , Smirnov Igor , Filiano Anthony J. , Shadowen Hannah M. , Cody Kris R. , Thompson Jeremy A. , Harris Tajie H. , Gaultier Alban , Overall Christopher C. , Kipnis Jonathan
Published: June 2018

Phagocytosis of synaptic material by microglia is critical for central nervous system development. Less well understood is this microglial function in the injured adult brain. Assay of microglial phagocytosis is challenging, because peripheral myeloid cells engraft the site of injury, which could obscure interpretation of microglial roles. The model used here, optic nerve crush injury, results in degeneration of synapses in the dorsal lateral geniculate nucleus (dLGN), which stimulates rapid activation and engulfment of synaptic material by resident microglia without myeloid cell engraftment. Pharmacological depletion of microglia causes postinjury accumulation of synaptic debris, suggesting that microglia are the dominant postinjury phagocytes. Genetic or pharmacological manipulations revealed that neuronal activity does not trigger microglia phagocytosis after injury. RNA sequencing reveals C1q and CD11b/CR3 involvement in clearance of debris by dLGN-resident microglia. Indeed, C1qa−/− and Itgam−/− mice exhibit impaired postinjury debris clearance. Our results show how neurodegenerative debris is cleared by microglia and offers a model for studying its mechanisms and physiological roles.
Gating currents
Authors: Bezanilla Francisco
Published: June 2018

Many membrane proteins sense the voltage across the membrane where they are inserted, and their function is affected by voltage changes. The voltage sensor consists of charges or dipoles that move in response to changes in the electric field, and their movement produces an electric current that has been called gating current. In the case of voltage-gated ion channels, the kinetic and steady-state properties of the gating charges provide information of conformational changes between closed states that are not visible when observing ionic currents only. In this Journal of General Physiology Milestone, the basic principles of voltage sensing and gating currents are presented, followed by a historical description of the recording of gating currents. The results of gating current recordings are then discussed in the context of structural changes in voltage-dependent membrane proteins and how these studies have provided new insights on gating mechanisms.
Impacts of Aerosols on Climate and Weather in the Hindu-Kush-Himalayas-Gangetic Region
Authors: Lau William K. M.
Published: June 2018

Situated at the southern edge of the Tibetan Plateau (TP), the Hindu-Kush-Himalayas-Gangetic (HKHG) region is under the clear and present danger of climate change. Flash-flood, landslide, and debris flow caused by extreme precipitation, as well as rapidly melting glaciers, threaten the water resources and livelihood of more than 1.2 billion people living in the region. Rapid industrialization and increased populations in recent decades have resulted in severe atmospheric and environmental pollution in the region. Because of its unique topography and dense population, the HKHG is not only a major source of pollution aerosol emissions, but also a major receptor of large quantities of natural dust aerosols transported from the deserts of West Asia and the Middle East during the premonsoon and early monsoon season (April–June). The dust aerosols, combined with local emissions of light-absorbing aerosols, that is, black carbon (BC), organic carbon (OC), and mineral dust, can (a) provide additional powerful heating to the atmosphere and (b) allow more sunlight to penetrate the snow layer by darkening the snow surface. Both effects will lead to accelerated melting of snowpack and glaciers in the HKHG region, amplifying the greenhouse warming effect. In addition, these light-absorbing aerosols can interact with monsoon winds and precipitation, affecting extreme precipitation events in the HKHG, as well as weather variability and climate change over the TP and the greater Asian monsoon region.
Meteorological History and Historical Climate of China
Authors: Fei Jie
Published: June 2018

The Chinese meteorological records could be traced back to the oracle-bone inscriptions of the Shang Dynasty (c. 1600 bc–c. 1046 bc). For the past 3,000 years, continuous meteorological records are available in official histories, chronicles, local gazetteers, diaries, and other historical materials. Ever since the Qin Dynasty (221–207 bc), precipitation reports to the central government were officially organized; however, only those of the Qing Dynasty (1644–1912 ad) are extant, and they have been widely used to reconstruct precipitation variability.

Modern meteorological knowledge began to be introduced in China during the late Ming Dynasty (1368–1644 ad). Modern meteorological observation possibly began in the 17th century, whereas continuous meteorological observation records go back to the mid-19th century.

Previous researches have reconstructed the chronologies of the temperature change in China during the past 2,000 years, and the Medieval Warm Period and Little Ice Age were identified. With regard to precipitation variability, yearly charts of dryness/wetness in China for the past 500 years were produced. Several chronologies of dust storm, plum rain (Meiyu), and typhoon were also established. Large volcanic eruptions resulted in short scale abrupt cooling in China during the past 2,000 years. Climatic change was significantly related to the war occurrences and dynastic cycles in historical China.
The Magnetosphere of Uranus
Authors: Cao Xin , Paty Carol
Published: June 2018

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Planetary Science. Please check back later for the full article.

A magnetosphere is formed by the interaction between the magnetic field of a planet and the high-speed solar wind. Those planets with a magnetosphere have an intrinsic magnetic field such as Earth, Jupiter, and Saturn. Mars, especially, has no global magnetosphere, but evidence shows that a paleo-magnetosphere existed billions of years ago and was dampened then due to some reasons such as the change of internal activity. A magnetosphere is very important for the habitable environment of a planet because it provides the foremost and only protection for the planet from the energetic solar wind radiation.

The majority of planets with a magnetosphere in our solar system have been studied for decades except for Uranus and Neptune, which are known as ice giant planets. This is because they are too far away from us (about 19 AU from the Sun), which means they are very difficult to directly detect. Compared to many other space detections to other planets, for example, Mars, Jupiter, Saturn and some of their moons, the only single fly-by measurement was made by the Voyager 2 spacecraft in the 1980s. The data it sent back to us showed that Uranus has a very unusual magnetosphere, which indicated that Uranus has a very large obliquity, which means its rotational axis is about 97.9° away from the north direction, with a relative rapid (17.24 hours) daily rotation. Besides, the magnetic axis is tilted 59° away from its rotational axis, and the magnetic dipole of the planet is off center, shifting 1/3 radii of Uranus toward its geometric south pole. Due to these special geometric and magnetic structures, Uranus has an extremely dynamic and asymmetric magnetosphere.

Some remote observations revealed that the aurora emission from the surface of Uranus distributed at low latitude locations, which has rarely happened on other planets. Meanwhile, it indicated that solar wind plays a significant impact on the surface of Uranus even if the distance from the Sun is much farther than that of many other planets. A recent study, using numerical simulation, showed that Uranus has a “Switch-like” magnetosphere that allows its global magnetosphere to open and close periodically with the planetary rotation.

In this article, we will review the historic studies of Uranus’s magnetosphere and then summarize the current progress in this field. Specifically, we will discuss the Voyager 2 spacecraft measurement, the ground-based and space-based observations such as Hubble Space Telescope, and the cutting-edge numerical simulations on it. We believe that the current progress provides important scientific context to boost future ice giant detection.
Female-to-Male Gender-Affirming Chest Reconstruction Surgery
Authors: Ammari Tareq , Sluiter Emily C , Gast Katherine , Kuzon William M
Published: June 2018

There is an increased demand for gender affirmation surgery. Chest contouring, or “top” surgery, is especially important in the female-to-male (FtM) transgender population. This Continuing Medical Education (CME) article critically appraises the available literature on top surgery to allow plastic surgeons to understand current practices and determine the best surgical technique using a decision algorithm and the patient’s preoperative anatomy and characteristics. Because a single best surgical approach does not exist due to significant variance in preoperative patient anatomy, and in order to provide a useful framework for decision making, surgical approaches described are categorized as: approach 1—remote incision procedures without skin excision; approach 2—procedures with periareolar skin excision; and approach 3—mastectomy procedures with skin excision other than periareolar skin excision. Decision algorithms that help determine the most suitable surgical technique for individual patients are reviewed. Data on complication rates and patient satisfaction will improve informed consent discussions and create realistic patient expectations.
Physiological RNA dynamics in RNA-Seq analysis
Authors: Xu Zhongneng , Asakawa Shuichi
Published: June 2018

Physiological RNA dynamics cause problems in transcriptome analysis. Physiological RNA accumulation affects the analysis of RNA quantification, and physiological RNA degradation affects the analysis of the RNA sequence length, feature site and quantification. In the present article, we review the effects of physiological degradation and accumulation of RNA on analysing RNA sequencing data. Physiological RNA accumulation and degradation probably led to such phenomena as incorrect estimations of transcription quantification, differential expressions, co-expressions, RNA decay rates, alternative splicing, boundaries of transcription, novel genes, new single-nucleotide polymorphisms, small RNAs and gene fusion. Thus, the transcriptomic data obtained up to date warrant further scrutiny. New and improved techniques and bioinformatics software are needed to produce accurate data in transcriptome research.
appreci8: a pipeline for precise variant calling integrating 8 tools
Authors: Sandmann Sarah , Karimi Mohsen , de Graaf Aniek O , Rohde Christian , Göllner Stefanie , Varghese Julian , Ernsting Jan , Walldin Gunilla , van der Reijden Bert A , Müller-Tidow Carsten , Malcovati Luca , Hellström-Lindberg Eva , Jansen Joop H , Dugas Martin
Published: June 2018

Motivation

The application of next-generation sequencing in research and particularly in clinical routine requires valid variant calling results. However, evaluation of several commonly used tools has pointed out that not a single tool meets this requirement. False positive as well as false negative calls necessitate additional experiments and extensive manual work. Intelligent combination and output filtration of different tools could significantly improve the current situation.

Results

We developed appreci8, an automatic variant calling pipeline for calling single nucleotide variants and short indels by combining and filtering the output of eight open-source variant calling tools, based on a novel artifact- and polymorphism score. Appreci8 was trained on two data sets from patients with myelodysplastic syndrome, covering 165 Illumina samples. Subsequently, appreci8’s performance was tested on five independent data sets, covering 513 samples. Variation in sequencing platform, target region and disease entity was considered. All calls were validated by re-sequencing on the same platform, a different platform or expert-based review. Sensitivity of appreci8 ranged between 0.93 and 1.00, while positive predictive value ranged between 0.65 and 1.00. In all cases, appreci8 showed superior performance compared to any evaluated alternative approach.

Availability and implementation

Appreci8 is freely available at https://hub.docker.com/r/wwuimi/appreci8/. Sequencing data (BAM files) of the 678 patients analyzed with appreci8 have been deposited into the NCBI Sequence Read Archive (BioProjectID: 388411; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA388411).

Supplementary information

Supplementary data are available at Bioinformatics online.
The Timing of Sensory-Guided Behavioral Response is Represented in the Mouse Primary Somatosensory Cortex
Authors: Camon Jérémy , Hugues Sandrine , Erlandson Melissa A , Robbe David , Lagoun Sabria , Marouane Emna , Bureau Ingrid
Published: June 2018

Whisker-guided decision making in mice is thought to critically depend on information processing occurring in the primary somatosensory cortex. However, it is not clear if neuronal activity in this “early” sensory region contains information about the timing and speed of motor response. To address this question we designed a new task in which freely moving mice learned to associate a whisker stimulus to reward delivery. The task was tailored in such a way that a wide range of delays between whisker stimulation and reward collection were observed due to differences of motivation and perception. After training, mice were anesthetized and neuronal responses evoked by stimulating trained and untrained whiskers were recorded across several cortical columns of barrel cortex. We found a strong correlation between the delay of the mouse behavioral response and the timing of multiunit activity evoked by the trained whisker, outside its principal cortical column, in layers 4 and 5A but not in layer 2/3. Circuit mapping ex vivo revealed this effect was associated with a weakening of layer 4 to layer 2/3 projection. We conclude that the processes controlling the propagation of key sensory inputs to naive cortical columns and the timing of sensory-guided action are linked.
Serological Evidence for the Circulation of Ebolaviruses in Pigs From Sierra Leone
Authors: Fischer Kerstin , Jabaty Juliet , Suluku Roland , Strecker Thomas , Groseth Allison , Fehling Sarah K , Balkema-Buschmann Anne , Koroma Bashiru , Schmidt Kristina M , Atherstone Christine , Weingartl Hana M , Mettenleiter Thomas C , Groschup Martin H , Hoenen Thomas , Diederich Sandra
Published: June 2018

Many human ebolavirus outbreaks have been linked to contact with wildlife including nonhuman primates and bats, which are assumed to serve as host species. However, it is largely unknown to what extent other animal species, particularly livestock, are involved in the transmission cycle or act as additional hosts for filoviruses. Pigs were identified as a susceptible host for Reston virus with subsequent transmission to humans reported in the Philippines. To date, there is no evidence of natural Ebola virus (EBOV) infection in pigs, although pigs were shown to be susceptible to EBOV infection under experimental settings. To investigate the potential role of pigs in the ecology of EBOV, we analyzed 400 porcine serum samples from Sierra Leone for the presence of ebolavirus-specific antibodies. Three samples reacted with ebolavirus nucleoproteins but had no neutralizing antibodies. Our results (1) suggest the circulation of ebolaviruses in swine in Sierra Leone that are antigenically related but not identical to EBOV and (2) could represent undiscovered ebolaviruses with unknown pathogenic and/or zoonotic potential.
Theorizing China’s rise in and beyond international relations
Authors: Pan Chengxin , Kavalski Emilian
Published: June 2018

China's rise, like the demise of the Soviet Union, is one of the defining events in the contemporary world. Yet, while the unexpected Soviet collapse and the end of the Cold War sparked the ‘Third Debate’ in International Relations (IR) theory, it is puzzling that the rise of China has yet to generate a comparable process of shell-shock and soul-searching among IR theorists. Just as the end of the Cold War is more than simply the end of a bipolar power struggle per se, so too China's rise is much more than the familiar ascendancy of another great power. Rather, it is also a complex, evolving and possibly border-traversing and paradigm-shattering phenomenon in global life that, on the one hand, requires fresh and innovative theorizing in and beyond IR and, on the other hand, potentially offers new insights for us to rethink world politics more broadly. This article introduces this Special Issue that seeks to tentatively respond to this theoretical, epistemological and ontological challenge. It draws attention to the blind spot in IR theorizing on China, and calls for deeper engagement between IR theory and China's rise that goes beyond mere ‘theory-testing’ within the existing perimeters of mainstream IR.
A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer
Authors: Fahrmann Johannes F , Bantis Leonidas E , Capello Michela , Scelo Ghislaine , Dennison Jennifer B , Patel Nikul , Murage Eunice , Vykoukal Jody , Kundnani Deepali L , Foretova Lenka , Fabianova Eleonora , Holcatova Ivana , Janout Vladimir , Feng Ziding , Yip-Schneider Michele , Zhang Jianjun , Brand Randall , Taguchi Ayumu , Maitra Anirban , Brennan Paul , Max Schmidt C , Hanash Samir
Published: June 2018

Background

We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC.

Methods

A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated.

Results

Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19–9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02).

Conclusions

A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
HISTONE DEACETYLASE 19 and the flowering time gene FD maintain reproductive meristem identity in an age-dependent manner
Authors: Gorham Sasha R , Weiner Aaron I , Yamadi Maryam , Krogan Naden T
Published: June 2018

Mutation of the chromatin regulator HDA19 causes age-dependent patterning defects in reproductive meristems. This effect is enhanced by mutation of FD, revealing a novel developmental role for this flowering time gene.
On the magnetic field of the first Galactic ultraluminous X-ray pulsar Swift J0243.6+6124
Authors: Tsygankov Sergey S , Doroshenko Victor , Mushtukov Alexander A , Lutovinov Alexander A , Poutanen Juri
Published: June 2018

We report on the monitoring of the final stage of the outburst from the first Galactic ultraluminous X-ray pulsar Swift J0243.6+6124, which reached ∼40 Eddington luminosities. The main aim of the monitoring program with the Swift/XRT telescope was to measure the magnetic field of the neutron star using the luminosity of transition to the ‘propeller’ state. The visibility constraints, unfortunately, did not permit us to observe the source down to the fluxes low enough to detect such a transition. The tight upper limit on the propeller luminosity Lprop < 6.8 × 1035 erg s−1 implies the dipole component of the magnetic field B < 1013 G. On the other hand, the observed evolution of the pulse profile and of the pulsed fraction with flux points to a change of the emission region geometry at the critical luminosity Lcrit ∼ 3 × 1038 erg s−1 both in the rising and declining parts of the outburst. We associate the observed change with the onset of the accretion column, which allows us to get an independent estimate of the magnetic field strength close to the neutron stars surface of B > 1013 G. Given the existing uncertainty in the effective magnetosphere size, we conclude that both estimates are marginally compatible with each other.
Interposing a varying gravitational constant between modified Newtonian dynamics and weak Weyl gravity
Authors: Christodoulou Dimitris M , Kazanas Demosthenes
Published: June 2018

The Newtonian gravitational constant G obeys the dimensional relation [G][M][a] = [$v$]4, where M, a, and $v$ denote mass, acceleration, and speed, respectively. Since the baryonic Tully-Fisher (BTF) and Faber-Jackson (BFJ) relations are observed facts, this relation implies that $G\, a={\rm constant}$. This result cannot be obtained in Newtonian dynamics which cannot explain the origin of the BTF and BFJ relations. An alternative, modified Newtonian dynamics (MOND) assumes that G = G0 is constant in space and derives naturally a characteristic constant acceleration a = a0, as well as the BTF and BFJ relations. This is overkill and it comes with a penalty: MOND cannot explain the origin of a0. A solid physical resolution of this issue is that G∝a−1, which implies that in lower-acceleration environments the gravitational force is boosted relative to its Newtonian value because G increases. This eliminates all problems related to MOND’s empirical cutoff a0 and yields a quantitative method for mapping the detailed variations of G(a) across each individual galaxy as well as on larger and smaller scales. On the opposite end, the large accelerations produced by G(a) appear to be linked to the weak-field limit of the fourth-order theory of conformal Weyl gravity.
Loss of BCAT1 Expression is a Sensitive Marker for IDH-Mutant Diffuse Glioma
Authors: Chen Yen-Ying , Ho Hsiang-Ling , Lin Shih-Chieh , Hsu Chih-Yi , Ho Donald Ming-Tak
Published: June 2018

BACKGROUND

IDH mutation is an important prognostic factor of diffuse astrocytomas. Although the majority of IDH mutations could be identified by immunohistochemical (IHC) stain for R132H-mutant IDH1, DNA sequencing would be required for IHC negative cases to determine their IDH mutation status. This approach is not cost-effective for tumors with low IDH mutation rates.

OBJECTIVE

To investigate whether BCAT1 could be used as a surrogate marker for IDH mutations, because BCAT1 is an enzyme related to IDH genes.

METHODS

A group of 120 anaplastic astrocytomas were immunostained for BCAT1, ATRX, and R132H-mutant IDH1. Staining results correlated with the results of DNA sequencing of IDH1/IDH2.

RESULTS

DNA sequencing showed IDH1/2 mutations in 50.8% of cases of which 73.8% had IDH1 R132H mutation. Several IDH1 noncodon 132 mutations, ie, G97D, S122N, G123E, I130K, and G131S, which had uncertain prognostic significance, were identified. IHC stain for R132H-mutant IDH1 identified 93.3% of IDH1 R132H mutations and 70.5% of all IDH mutations. BCAT1 loss was seen in 65.8% of cases, its sensitivity to identify IDH mutations was 96.7%. The sensitivity reached 100% for IDH1 codon 132 and IDH2 codon 172 mutations.

CONCLUSION

Positive BCAT1 stain could be used to exclude diffuse gliomas with IDH1 codon 132 and IDH2 codon 172 mutations. Selecting cases with negative BCAT1 and R132H-mutant IDH1 staining for DNA sequencing of IDH1/2 genes could improve the cost-effectiveness of detecting IDH mutations particularly in tumors with low IDH mutation rates, and confine the need of 1p/19q assay in IDH-mutant tumors.
Oxytocin‐like signaling in ants influences metabolic gene expression and locomotor activity
Authors: Liutkevičiūte Zita , Gil‐Mansilla Esther , Eder Thomas , Casillas‐Pérez Barbara , Di Giglio Maria Giulia , Muratspahić Edin , Grebien Florian , Rattei Thomas , Muttenthaler Markus , Cremer Sylvia , Gruber Christian W.
Published: June 2018

Ants are emerging model systems to study cellular signaling because distinct castes possess different physiologic phenotypes within the same colony. Here we studied the functionality of inotocin signaling, an insect ortholog of mammalian oxytocin (OT), which was recently discovered in ants. InLasiusants, we determined that specialization within the colony, seasonal factors, and physiologic conditions down‐regulated the expression of the OT‐like signaling system. Given this natural variation, we interrogated its function using RNAi knockdowns. Next‐generation RNA sequencing of OT‐like precursor knock‐down ants highlighted its role in the regulation of genes involved in metabolism. Knock‐down ants exhibited higher walking activity and increased self‐grooming in the brood chamber. We propose that OT‐like signaling in ants is important for regulating metabolic processes and locomotion.—Liutkevičiūtė, Z., Gil‐Mansilla, E., Eder, T., Casillas‐Pérez, B., Di Giglio, M. G., Muratspahić, E., Grebien, F., Rattei, T., Muttenthaler, M., Cremer, S., Gruber, C. W. Oxytocin‐like signaling in ants influences metabolic gene expression and locomotor activity.FASEB J.32, 6808–6821 (2018).www.fasebj.org
Lymph Node Yield After Neoadjuvant Chemoradiotherapy in Rectal Cancer Specimens: A Randomized Trial Comparing Two Fixatives
Authors: Dias Andre R. , Pereira Marina Alessandra , de Mello Evandro Sobroza , Nahas Sergio Carlos , Cecconello Ivan , Ribeiro Ulysses
Published: June 2018

BACKGROUND:

It is widely reported that neoadjuvant chemoradiation reduces lymph node yield in rectal cancer specimens. Some have questioned the adequacy of finding ≥12 lymph nodes for accurate staging, and fewer nodes were correlated with good response. Others reported that low lymph node count raises the chance for understaging and correlates with worse survival. In addition, a few studies demonstrated that diligent specimen analysis increases lymph node count.

OBJECTIVE:

The aim of this study was to compare Carnoy’s solution and formalin concerning lymph node yield in specimens of patients with rectal cancer after neoadjuvant chemoradiation.

DESIGN:

This is a prospective randomized trial that was conducted from 2012 to 2015.

SETTINGS:

This study was performed in a reference cancer center in Brazil.

PATIENTS:

Patients who underwent low anterior resection with total mesorectal excision after neoadjuvant chemoradiation for rectal adenocarcinoma were included.

INTERVENTION:

Rectosigmoid specimens were randomized for fixation with Carnoy’s solution or formalin.

MAIN OUTCOME MEASURES:

A total of 130 specimens were randomized. After dissection, the residual fat from the formalin group was immersed in Carnoy’s solution in search for missed lymph nodes (Revision).

RESULTS:

The Carnoy’s solution group had superior lymph node count (24.0 vs 16.3, p < 0.01) and fewer cases with <12 lymph nodes (6 vs 22, p = 0.001). The Revision group found lymph nodes in all cases (mean, 11.1), retrieving metastatic lymph nodes in 6 patients. It reduced the formalin cases with <12 lymph nodes from 33.8% to 4.6% and upstaged 2 patients. Tumor response to neoadjuvant chemoradiotherapy was not associated with lymph node count.

LIMITATIONS:

This was a unicentric study.

CONCLUSIONS:

Compared with formalin, the Carnoy’s solution increases lymph node count and reduces the cases with <12 lymph nodes. Harvested lymph nodes are missed following routine analysis and this is clinically relevant. Finding <12 lymph nodes is not a sign of good response to neoadjuvant chemoradiation (www.clinicaltrials.gov. Unique identifier: NCT02629315). See Video Abstract at http://links.lww.com/DCR/A694.