bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC11 regulates type I interferon signaling through defatty-acylation of SHMT2
Authors: Cao Ji , Sun Lei , Aramsangtienchai Pornpun , Spiegelman Nicole A. , Zhang Xiaoyu , Huang Weishan , Seto Edward , Lin Hening
Published: March 2019

Significance

HDAC11 is the only class IV member of the histone deacetylase (HDAC) family, and very little is known about its biological function. The work here reveals its efficient and physiologically relevant activity. The regulation of SHMT2 and interferon signaling expands the known biological function of protein lysine fatty acylation, which has only recently started to be appreciated. Furthermore, a compelling molecular mechanism is proposed to connect HDAC11 to immune response. The finding opens exciting opportunities to develop HDAC11-specific inhibitors to treat human diseases that would benefit from increased type I interferon signaling, such as viral infection, multiple sclerosis, and cancer.
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis
Authors: Zheng Yu , Comaills Valentine , Burr Risa , Boulay Gaylor , Miyamoto David T. , Wittner Ben S. , Emmons Erin , Sil Srinjoy , Koulopoulos Michael W. , Broderick Katherine T. , Tai Eric , Rengarajan Shruthi , Kulkarni Anupriya S. , Shioda Toshi , Wu Chin-Lee , Ramaswamy Sridhar , Ting David T. , Toner Mehmet , Rivera Miguel N. , Maheswaran Shyamala , Haber Daniel A.
Published: March 2019

Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single-cell RNA sequencing in an orthotopic mouse prostate cancer model, we find up-regulation of prolactin receptor as cancer cells that have disseminated to the lungs expand into micrometastases. Secretion of the ligand prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E2 (PGE2). PGE2 treatment of fibroblasts activates the orphan nuclear receptor NR4A (Nur77), with prolactin as a major transcriptional target for the NR4A-retinoid X receptor (RXR) heterodimer. Ectopic expression of prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor celecoxib abrogates prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, prolactin, and prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine cross-talk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression.
Stepwise 5′ DNA end-specific resection of DNA breaks by the Mre11-Rad50-Xrs2 and Sae2 nuclease ensemble
Authors: Cannavo Elda , Reginato Giordano , Cejka Petr
Published: March 2019

Significance

The Mre11-Rad50-Xrs2 (MRX)-Sae2 complex has key functions in initiating the repair of DNA double-strand breaks by homologous recombination. Using purified recombinant proteins, we demonstrate how ATP binding and hydrolysis by the Rad50 subunit regulate the nuclease activities of Mre11. We reconstitute a reaction wherein the MRX-Sae2 ensemble preferentially degrades the 5′-terminated DNA strands at DNA break sites up to several hundred nucleotides in length. This polarity of DNA end processing is required for homologous recombination. Our experiments help explain how MRX-Sae2 and their homologs contribute to the maintenance of genome stability.
Encoding biological recognition in a bicomponent cell-membrane mimic
Authors: Rodriguez-Emmenegger Cesar , Xiao Qi , Kostina Nina Yu. , Sherman Samuel E. , Rahimi Khosrow , Partridge Benjamin E. , Li Shangda , Sahoo Dipankar , Reveron Perez Aracelee M. , Buzzacchera Irene , Han Hong , Kerzner Meir , Malhotra Ishita , Möller Martin , Wilson Christopher J. , Good Matthew C. , Goulian Mark , Baumgart Tobias , Klein Michael L. , Percec Virgil
Published: March 2019

Significance

The seminal fluid mosaic model of the cell membranes suggests a lipid bilayer sea, in which cholesterol, proteins, glycoconjugates, and other components are swimming. Complementing this view, a microsegregated rafts model predicts clusters of components that function as relay stations for intracellular signaling and trafficking. However, elucidating the arrangement of glycoconjugates responsible for communication and recognition between cells, and cells with proteins remains a challenge. Herein, designed dendritic macromolecules are shown to self-assemble into vesicles that function as biological-membrane mimics with controlled density of sugar moieties on their periphery. Surprisingly, lowering sugar density elicits higher bioactivity to sugar-binding proteins. This finding informs a design principle for active complex soft matter with potential for applications in cellular biology and nanomedicine.
Regional effects of climate change on California animal agriculture and options for farmers to respond through husbandry adaptation and greenhouse gas mitigation.
Authors: Pitesky M. , James J. , Pandey P. , Mitloehner F. , Cadena M. , Aly S.
Published: March 2019

Climate change will pose challenges for the world's food supply in the coming decades. As a leading agricultural state with a diverse agricultural portfolio, California will face its own unique regional challenges due to its complex agricultural inter-dependencies. As veterinarians and animal scientists with livestock and poultry clientele in the Central Valley of California, we are starting to observe changes in food safety, production efficiency, welfare and disease that can be linked to the effects of climate change. For example, in California drought has reduced access to rice hulls which are commonly used as bedding for poultry which have necessitated the use for recycling rice hulls. Our results have shown an 11.08 ÃÂ greater risk (
P
<0.5) of Salmonella in poultry raised on litter recycled more than 3 ÃÂ versus poultry raised on fresh litter material. While these types of challenges can be mitigated through adapting husbandry, it is also important to recognize that there are opportunities for the farmers to focus on mitigation of greenhouse gases via the alternative usage of agricultural 'waste' products with a focus on increasing baseload renewable energy from anaerobic digestion (AD). Specifically, the further targeted integration of methane digesters in the Central Valley of California could play a significant role in renewable energy production from carbon-based agricultural 'waste' material. To that point, geographic information system-based maps were made showing the spatial location of major livestock and crop production areas laid over the current natural gas pipeline network for Fresno County (the most productive agricultural county in the USA). Refinement and further development of these types of maps are integral in order to visualize and develop a robust and commercially viable AD network into our current energy infrastructure. This review aims to describe current scenarios spanning food safety, welfare and the connection between animal disease and production efficiency in California livestock and poultry production with respect to how climate change affects California livestock and poultry.
Monsoon variability trends and strategies to get through its vagaries in rice-based systems in eastern India.
Authors: Panneerselvam P. , Sudhanshu Singh Sudhanshu Singh
Published: March 2019

The trend of increasing monsoon variability in eastern India has led to increased risk of growing crops during the monsoon period. The rainfall pattern has become more erratic due to the shrinking of monsoon period 60-70 days from the normal 120 days, leading to drought and unusual frequent torrential rainfall exceeding 200-250 mm/day, causing floods during the past few decades. The duration and magnitude of drought and the number of dry spells also have increased. These stresses not only affect the yield of rice but also reduce the area and production of succeeding crops, resulting in low system productivity. Rice is the major crop in monsoon season in eastern India. Hence, technological or management options to cope with monsoon variability are discussed based on the available literature and results from the experiments conducted in eastern India, particularly in Odisha. Direct seeded rice (DSR) is an apt option for delayed onset of the monsoon that enables better use of early rains. In this regard, DSR helps reduce the risk of-of late-season drought by avoiding the stress period. Thus, DSR allows farmers to undertake early sowing of the subsequent crops, leading to higher system productivity. The performance of short-duration drought- and flood-tolerant rice varieties in stress-prone areas are reviewed and discussed here. Rice nursery enterprise in private- as well as community-sector has been proved as an effective strategy to ensure timely availability of healthy seedlings. However, the scale of these technologies/management options in eastern India is facing a tough challenge due to weed infestation, lack of availability of tolerant anaerobic and stagnant flood varieties, and appropriate machinery, in addition to socio-economic constraints to access the technologies.
Debunking, supervenience, and Hume’s Principle
Authors: Leng Mary
Published: March 2019

Debunking arguments against both moral and mathematical realism have been pressed, based on the claim that our moral and mathematical beliefs are insensitive to the moral/mathematical facts. In the mathematical case, I argue that the role of Hume’s Principle as a conceptual truth speaks against the debunkers’ claim that it is intelligible to imagine the facts about numbers being otherwise while our evolved responses remain the same. Analogously, I argue, the conceptual supervenience of the moral on the natural speaks presents a difficulty for the debunker’s claim that, had the moral facts been otherwise, our evolved moral beliefs would have remained the same.
Search for transcription factors affecting productivity of the polyketide FR901512 in filamentous fungal sp. No. 14919 and identification of Drf1, a novel negative regulator of the biosynthetic gene cluster
Authors: Itoh Hiroya , Miura Ai , Takeda Itaru , Matsui Makoto , Tamano Koichi , Machida Masayuki , Shibata Takashi
Published: March 2019

In order to increase secondary metabolite production in filamentous fungi, a transcription factor gene in the biosynthetic gene cluster and global regulator genes such as laeA are considered plausible as targets for overexpression by genetic modification. In this study, we examined these overexpression effect in fungal sp. No. 14919 that produces FR901512, an HMG-CoA reductase inhibitor. Resultantly, the productivity was improved at 1.7–1.8 fold by overexpressing frlE, a transcription factor gene in the biosynthetic gene cluster, whereas productivity did not change by overexpression of laeA and veA. Furthermore, we searched for extra transcription factors affecting the productivity by transcriptome analysis between wild-type strain and highly productive UV mutants. After verifying productivity decrease by overexpression, Drf1, a novel transcription factor encoded by drf1 was identified as the negative regulator. Because each frlE product (FrlE) and Drf1 worked on the same cluster in positive and negative regulatory manners, their network was analyzed.
Aggregation of Lactobacillus brevis associated with decrease in pH by glucose fermentation
Authors: Saito Katsuichi , Tomita Satoru , Nakamura Toshihide
Published: March 2019

Some Lactobacillus brevis strains were found to aggregate upon the addition of glucose, which resulted in glucose fermentation and pH decrease. Surface layer proteins (Slp) that represented the outermost layer of the bacteria decreased under these low pH conditions, probably because of the partial detachment of Slp from the cell surface triggered by the acidic environment. Similar observations of decreased Slp and aggregation were observed under the culture conditions, confirming that L. brevis aggregation was due to the partial Slp detachment under the acidic conditions of glucose fermentation. Such Slp detachment might affect the electrostatic nature of L. brevis cells by initiating the formation of irregular charge across the L. brevis cell surface, thereby leading to aggregation. These observations would be useful for elucidating the aggregation mechanism of lactic acid bacteria, which was considered to be involved in the probiotic effect of the bacteria.
The time course of muscle‐tendon properties and function responses of a five‐minute static stretching exercise
Authors: Konrad A. , Reiner M. M. , Thaller S. , Tilp M.
Published: March 2019

The purpose of this study was to investigate the time course of the changes of muscle‐tendon mechanical properties and the function responses of the plantar flexor muscles following 5 × 60 s of static stretching.

Fourteen healthy volunteers were tested on four separate days in a random order with three different rest times (0, 5, 10 min) after 5 × 60 s of stretching or following a control period without stretching. During each test, the dorsiflexion range of motion (RoM), passive resistive torque (PRT), and maximum voluntary contraction (MVC) were measured with a dynamometer. Ultrasonography of the gastrocnemius medialis (GM) muscle‐tendon junction displacement and motion capture allowed us to determine the length changes in the tendon and muscle, respectively, and hence to calculate their stiffness.

We observed an increase in RoM and decrease in MVC at 0, 5, and 10 min post‐stretching. This could be attributed to an increase in muscle elongation which lasted at least 10 min. A decrease in muscle‐tendon stiffness was observed immediately, but not 5 or 10 min after the stretching. A decrease in PRT and muscle stiffness was observed up to 5 min after the stretching. No changes were detected in tendon stiffness or in any variable in the control group.

The effects of a 5 × 60 s static stretching exercise changes the muscle‐tendon functions (RoM, MVC), which are related to mechanical changes of the muscle but not the tendon structure, respectively. Although the functional changes last for at least 10 min, changes in muscle stiffness were only observed up to 5 min after the stretching exercise.
Has the prose quality of science textbook improved over the past decade? A linguistic perspective
Authors: Zhu Shan , Fang Zhihui
Published: March 2019

Textbooks are a central pedagogical resource for science teachers. As such, they have been a subject of enduring interest in science education research, with many questioning whether their quality has improved over the past decades. In this paper, we examined the prose quality of an expository text on coral reefs in seven successive editions of one popular environmental science textbook. Specifically, using tools from systemic functional linguistics, we analyzed two discursive aspects that impact the comprehensibility of the texts – how causation is construed and how information is structured. Our analyses reveal that the prose quality of the texts on coral reefs has improved, regressed, or remained the same. In the area of causation, cause–effect relationships are construed in increasingly implicit ways, with causes and effects consistently constructed as grammatical abstractions that bury human or social agencies. In the area of information flow, semantic leaps and semantic ambiguities are reduced across the sample texts analyzed, which places fewer text processing demands on the reader. Our study suggests that writing a perfectly considerate text is a tall task and that micro-linguistic analysis can illuminate the comprehension challenges that school textbooks present to students and inform efforts to improve students’ science literacy.
The growing threat of heat disasters
Authors: Sailor David J , Baniassadi Amir , O’Lenick Cassandra R , Wilhelmi Olga V
Published: March 2019

Heat is the number one weather-related killer in the United States and indoor exposure is responsible for a significant portion of the resulting fatalities. Evolving construction practices combined with urban development in harsh climates has led building occupants in many cities to rely on air conditioning (AC) to a degree that their health and well-being are compromised in its absence. The risks are substantial if loss of AC coincides with a hot weather episode (henceforth, a heat disaster). Using simulations, we found that residential buildings in many US cities are highly vulnerable to heat disasters—with more than 50 million citizens living in cities at significant risk. This situation will be exacerbated by intensification of urban heat islands, climate change, and evolving construction practices. It is therefore crucial that future building codes consider thermal resiliency in addition to energy efficiency.
Hypernodulating soybean mutant line nod4 lacking ‘Autoregulation of Nodulation’ (AON) has limited root-to-shoot water transport capacity
Authors: Caroline Silva Lopes Emile , Pereira Rodrigues Weverton , Ruas Fraga Katherine , Machado Filho José Altino , Rangel da Silva Jefferson , Menezes de Assis-Gomes Mara , Moura Assis Figueiredo Fabio Afonso Mazzei , Gresshoff Peter M , Campostrini Eliemar
Published: March 2019

Background and Aims

Although hypernodulating phenotype mutants of legumes, such as soybean, possess a high leaf N content, the large number of root nodules decreases carbohydrate availability for plant growth and seed yield. In addition, under conditions of high air vapour pressure deficit (VPD), hypernodulating plants show a limited capacity to replace water losses through transpiration, resulting in stomatal closure, and therefore decreased net photosynthetic rates. Here, we used hypernodulating (nod4) (282.33 ± 28.56 nodules per plant) and non-nodulating (nod139) (0 nodules per plant) soybean mutant lines to determine explicitly whether a large number of nodules reduces root hydraulic capacity, resulting in decreased stomatal conductance and net photosynthetic rates under high air VPD conditions.

Methods

Plants were either inoculated or not inoculated with Bradyrhizobium diazoefficiens (strain BR 85, SEMIA 5080) to induce nitrogen-fixing root nodules (where possible). Absolute root conductance and root conductivity, plant growth, leaf water potential, gas exchange, chlorophyll a fluorescence, leaf ‘greenness’ [Soil Plant Analysis Development (SPAD) reading] and nitrogen content were measured 37 days after sowing.

Key Results

Besides the reduced growth of hypernodulating soybean mutant nod4, such plants showed decreased root capacity to supply leaf water demand as a consequence of their reduced root dry mass and root volume, which resulted in limited absolute root conductance and root conductivity normalized by leaf area. Thereby, reduced leaf water potential at 1300 h was observed, which contributed to depression of photosynthesis at midday associated with both stomatal and non-stomatal limitations.

Conclusions

Hypernodulated plants were more vulnerable to VPD increases due to their limited root-to-shoot water transport capacity. However, greater CO2 uptake caused by the high N content can be partly compensated by the stomatal limitation imposed by increased VPD conditions.
Lack of Toxicity With Long-term Isavuconazole Use in Patients With Hematologic Malignancy
Authors: DiPippo Adam J , Kontoyiannis Dimitrios P
Published: March 2019

Prolonged courses of isavuconazole (ISA) are increasingly utilized in immunocompromised patients. Toxicities have been reported with long-term use of the other triazoles. We report the first real-life tolerability data in 50 patients with hematologic malignancy receiving ≥6 months of ISA. ISA was well tolerated in our ill patient population.
Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury
Authors: Sonnenschein Kristina , Fiedler Jan , Pfanne Angelika , Just Annette , Mitzka Saskia , Geffers Robert , Pich Andreas , Bauersachs Johann , Thum Thomas
Published: March 2019

Aims

Delayed re-endothelialization after balloon angioplasty in patients with coronary or peripheral artery disease impairs vascular healing and leads to neointimal proliferation. In the present study, we examined the effect of RNA-binding motif protein 38 (Rbm38) during re-endothelialization in a murine model of experimental vascular injury.

Methods and results

Left common carotid arteries of C57BL/6 mice were electrically denudated and endothelial regeneration was evaluated. Profiling of RNA-binding proteins revealed dysregulated expression of Rbm38 in the denudated and regenerated areas. We next tested the importance of Rbm38 in human umbilical vein endothelial cells (HUVECS) and analysed its effects on cellular proliferation, migration and apoptosis. Rbm38 silencing in vitro demonstrated important beneficial functional effects on migratory capacity and proliferation of endothelial cells. In vivo, local silencing of Rbm38 also improved re-endothelialization of denuded carotid arteries. Luciferase reporter assay identified miR-98 and let-7f to regulate Rbm38 and the positive proliferative properties of Rbm38 silencing in vitro and in vivo were mimicked by therapeutic overexpression of these miRNAs.

Conclusion

The present data identified Rbm38 as an important factor of the regulation of various endothelial cell functions. Local inhibition of Rbm38 as well as overexpression of the upstream regulators miR-98 and let-7f improved endothelial regeneration in vivo and thus may be a novel therapeutic entry point to avoid endothelial damage after balloon angioplasty.
Early Dose Optimisation of Golimumab in Nonresponders to Induction Treatment for Ulcerative Colitis Is Effective and Supported by Pharmacokinetic Data
Authors: Philip George , Cornillie Freddy , Adedokun J Omoniyi , Melsheimer Richard , Rutgeerts Paul , Colombel Jean-Frédéric , Marano Colleen
Published: March 2019

Background and Aims

In nonresponders to golimumab induction for ulcerative colitis, we assessed clinical response rates and golimumab serum concentrations when the 100-mg dose was used early in the course of maintenance.

Methods

This post-hoc analysis of golimumab maintenance dosing [in the PURSUIT-M study] examined clinical outcomes and golimumab concentrations in early [Week 6] responders and nonresponders to induction, including subgroups based on body weight.

Results

In nonresponders to golimumab induction [assessed at Week 6], the 100-mg maintenance dose [starting at Week 6] resulted in a meaningful proportion [28.1%] of patients achieving a partial Mayo response at Week 14. After 1 year of maintenance, clinical outcome [response, remission, mucosal healing, corticosteroid-free state] rates in these “late” [Week 14] responders were similar to those in early [Week 6] responders. Golimumab concentrations in early nonresponders were approximately half those of early responders, suggesting that early nonresponders had more rapid golimumab clearance. Examined by body weight, the early nonresponders weighing <80 kg and receiving 100 mg had golimumab concentrations similar to the early responders [weighing <80 kg or ≥80 kg and receiving 50 mg or 100 mg, respectively].

Conclusions

Early use of the 100-mg maintenance dose leads to positive clinical outcomes in a meaningful proportion of patients who did not respond to golimumab at Week 6. Early nonresponders <80 kg who received the 100-mg maintenance dose achieved adequate golimumab concentrations and a clinically meaningful proportion of these patients had a late clinical response.

PURSUIT-M protocol number C0524T18; ClinicalTrials.gov, NCT00488631; EudraCT, 2006-003399-37.
Do individual surgeon volumes affect outcomes in thoracic surgery?†
Authors: Harrison Sebron , Sun Tiany , Kamel Mohamed K , Cleary Corbin , Stiles Brendon M , Altorki Nasser K , Sedrakyan Art
Published: March 2019

OBJECTIVES:

Minimum volume standards for thoracic surgical procedures have been advocated to improve outcomes. However, such standards are controversial within the thoracic surgery literature, and the methodology to determine cut points between high- and low-volume hospitals has been criticized. Furthermore, while multiple studies have examined hospital volume and its relationship with outcomes, there have been very few attempts to study this issue from the perspective of the individual thoracic surgeon. The aim of this study was to determine if surgeon volume is associated with differences in outcomes using a large state-wide database.

METHODS:

The study utilized the New York State Department of Health Statewide Planning and Research Cooperative (SPARCS) data for analysis. Patients who underwent major lung resections including sublobar resection, lobectomy and pneumonectomy from 1995 to 2014 were included and were categorized into 3 subgroups based on the extent of resection. Patient characteristics included age, gender, race, insurance and comorbidities. Surgeon information was obtained by using a unique identifier. Average annual surgical volumes of sublobar resection, lobectomy and pneumonectomy were calculated separately and grouped into 3 categories based on the tertiles. Demographic data and comorbidities were compared between the various volume groups to analyse the resulting complications. Primary outcomes were in-hospital mortality and 30-day readmission.

RESULTS:

There were a total of 99 576 major lung resections performed between 1995 and 2014 in the SPARCS database. Among these, the majority were wedge or segmental resections (n = 54 953, 55.2%) followed by lobectomy (n = 40 421, 40.6%) and pneumonectomy (n = 4202, 4.2%). In-hospital mortality was significantly greater for low-volume surgeons compared to high-volume surgeons for all resection groups. Additionally, low-volume surgeons had higher 30-day readmission rates for patients undergoing lobectomy and pneumonectomy. However, low-volume surgeons as a group were more likely to operate on black patients and patients with Medicaid, and black race was an independent predictor of mortality across all resection groups. The vast majority of surgeons performing lobectomy (89.5%) were in the low-volume group.

CONCLUSIONS:

Low-volume surgeons had higher rates of in-hospital mortality compared to their high-volume counterparts. However, the vast majority of surgeons performing lobectomy (89.5%) were in the low-volume group, and low-volume surgeons operated on higher percentages of black patients. These findings suggest that minimal volume standards would significantly impact the current delivery of thoracic surgery in the US.
Common workflow language (CWL)-based software pipeline for de novo genome assembly from long- and short-read data
Authors: Korhonen Pasi K , Hall Ross S , Young Neil D , Gasser Robin B
Published: March 2019

Background

Here, we created an automated pipeline for the de novoassembly of genomes from Pacific Biosciences long-read and Illumina short-read data using common workflow language (CWL). To evaluate the performance of this pipeline, we assembled the nuclear genomes of the eukaryotes Caenorhabditis elegans (~100 Mb), Drosophila melanogaster (~138 Mb), and Plasmodium falciparum (~23 Mb) directly from publicly accessible nucleotide sequence datasets and assessed the quality of the assemblies against curated reference genomes.

Findings

We showed a dependency of the accuracy of assembly on sequencing technology and GC content and repeatedly achieved assemblies that meet the high standards set by the National Human Genome Research Institute, being applicable to gene prediction and subsequent genomic analyses.

Conclusions

This CWL pipeline overcomes current challenges of achieving repeatability and reproducibility of assembly results and offers a platform for the re-use of the workflow and the integration of diverse datasets. This workflow is publicly available via GitHub (https://github.com/vetscience/Assemblosis) and is currently applicable to the assembly of haploid and diploid genomes of eukaryotes.
Absenteeism in the Public and the Private Sector: Does the Public Sector Attract High Absence Employees?
Authors: Mastekaasa Arne
Published: March 2019

Evidence from many countries shows that public sector employees have considerably higher rates of absenteeism than have private sector employees. Based on regression analyses of a large probability sample of the Norwegian population, this article shows that most of the sector difference in long-term absence can be accounted for by taking into consideration the sociodemographic characteristics of the workforce and the occupational composition in the two sectors. A clear sector difference in short-term absenteeism cannot be accounted for in this way. A direct effect of the working or employment conditions in the two sectors is also not a likely explanation, since workers who switch between the sectors are not more absent when they are in the public than when they are in the private sector. Thus, the high level of short-term absenteeism in the public sector seems to be due to a selection of absence-prone individuals to the sector. Since motivational factors are likely to be relatively more important for short-term than for long-term, these findings indicate that lower work attendance motivation in public sector employees may be the main driver. These patterns are consistent with an economic explanation in which people with low attendance motivation select to the public sector, since the work attendance incentives are weaker there. The degree to which the results are compatible with the theory public service motivation is also discussed.
Testing general relativity using binary extreme-mass-ratio inspirals
Authors: Han Wen-Biao , Chen Xian
Published: March 2019

It is known that massive black holes (MBHs) of $10^{5-7}\, \mathrm{ M}_\odot$ could capture small compact objects to form extreme-mass-ratio inspirals (EMRIs). Such systems emit gravitational waves (GWs) in the band of the Laser Interferometer Space Antenna (LISA) and are ideal probes of the space–time geometry of MBHs. Recently, we have shown that MBHs could also capture stellar-mass binary black holes (about $10\, \mathrm{ M}_\odot$) to form binary-EMRIs (b-EMRIs) and, interestingly, a large fraction of the binaries coalesce due to the tidal perturbation by the MBHs. Here we further show that the coalescence could be detected by LISA as glitches in EMRI signals. We propose an experiment to use the multiband (102 and 10−3 Hz) glitch signals to test gravity theories. Our simulations suggest that the experiment could measure the mass and linear momentum lost via GW radiation, as well as constrain the mass of gravitons, to a precision that is one order of magnitude better than the current limit.
The distance, supernova rate, and supernova progenitors of NGC 6946
Authors: Eldridge J J , Xiao Lin
Published: March 2019

The distance to the fireworks galaxy NGC 6946 is highly uncertain. Recent distance estimates using the tip of the red giant branch of 7.7 to 7.8 Mpc are larger than the distance commonly assumed for studying supernovae in this galaxy of 5.9 Mpc. Here we use the high supernova rate of the galaxy to derive the star formation rate and predict the galaxy’s FUV flux. We also account for dust extinction by different methods to derive a distance of 7.9 ± 4.0 Mpc for NGC 6946. We then use the new distance to re-evaluate the understanding of the supernova progenitors 2002hh, 2004et, 2017eaw, the possible electron capture event 2008S, and the possible black hole forming event N6946-BH1. For the latter two exotic events the new distance improves the consistency between the observed progenitors and the stellar models that give rise to these events. From our findings we strongly recommend that all future studies of NGC 6946 must use the greater distance to the galaxy of 7.72 ± 0.32 Mpc of Anand, Rizzi & Tully (2018).
The Emerging Role of Biomarkers in Adaptive Modulation of Clinical Brain Stimulation
Authors: Hoang Kimberly B , Turner Dennis A
Published: March 2019

Therapeutic brain stimulation has proven efficacious for treatment of nervous system diseases, exerting widespread influence via disease-specific neural networks. Activation or suppression of neural networks could theoretically be assessed by either clinical symptom modification (ie, tremor, rigidity, seizures) or development of specific biomarkers linked to treatment of symptomatic disease states. For example, biomarkers indicative of disease state could aid improved intraoperative localization of electrode position, optimize device efficacy or efficiency through dynamic control, and eventually serve to guide automatic adjustment of stimulation settings. Biomarkers to control either extracranial or intracranial stimulation span from continuous physiological brain activity, intermittent pathological activity, and triggered local phenomena or potentials, to wearable devices, blood flow, biochemical or cardiac signals, temperature perturbations, optical or magnetic resonance imaging changes, or optogenetic signals. The goal of this review is to update new approaches to implement control of stimulation through relevant biomarkers. Critical questions include whether adaptive systems adjusted through biomarkers can optimize efficiency and eventually efficacy, serve as inputs for stimulation adjustment, and consequently broaden our fundamental understanding of abnormal neural networks in pathologic states. Neurosurgeons are at the forefront of translating and developing biomarkers embedded within improved brain stimulation systems. Thus, criteria for developing and validating biomarkers for clinical use are important for the adaptation of device approaches into clinical practice.
The Effectiveness of Percutaneous Balloon Compression, Thermocoagulation, and Glycerol Rhizolysis for Trigeminal Neuralgia in Multiple Sclerosis
Authors: Noorani Imran , Lodge Amanda , Vajramani Girish , Sparrow Owen
Published: March 2019

BACKGROUND

Balloon compression (BC), thermocoagulation (TC), and glycerol rhizolysis (GR) are percutaneous surgical options for trigeminal neuralgia (TN). Whether the outcomes of these procedures in multiple sclerosis -related TN (MS-TN) are as effective as in idiopathic TN (ITN) is unknown.

OBJECTIVE

To retrospectively compare pain relief, complications, and durability achieved by these 3 types of procedures in MS-TN and ITN.

METHODS

Two hundred and four patients with typical TN were treated percutaneously: 33 had MS-TN (64 procedures) and 171 had ITN (329 procedures). All were performed by 1 of 2 neurosurgeons; interviews enabled long-term data to be gathered by an independent observer.

RESULTS

MS-TN patients (53.1%) had Barrow Neurological Institute pain scores of I or II after a percutaneous procedure, compared with 59.3% in the ITN cohort; there was no difference in initial relief between the 2 groups overall (P = .52). There was a trend toward fewer complications in MS-TN compared with ITN (23.4% vs 33.7%, respectively; P = .058). Kaplan–Meier analysis demonstrated no difference in durability of relief in MS-TN (median 23.0 mo) compared with ITN overall (median 24.0 mo; P = .75). Subgroup analysis demonstrated longer relief from BC and TC compared with GR in MS-TN (P = .013). Multivariate analysis confirmed that although the presence of MS does not predict durability of outcome, postoperative numbness (P = .0046) and undergoing a repeat procedure (P = .037) were significant predictors.

CONCLUSION

BC and TC are safe and effective in MS-TN. Postoperative numbness is the strongest prognostic factor in MS-TN.
The Politics of Peace
Authors: Goedde Petra
Published: March 2019

This study explores the emerging politics of peace, both as an ideal and as a pragmatic aspect of international relations during the early Cold War. By tracing the myriad ways in which a broad spectrum of people involved in and affected by the Cold War used, altered, and fought over this seemingly universal concept, it deconstructs the assumed binary between realist and idealist foreign policy approaches generally accepted among contemporary policymakers. It argues that a politics of peace emerged in the 1950s and 1960s as a result of a gradual convergence between idealism and realism. A transnational politics of peace succeeded only when idealist objectives met the needs of realist political ambition. It maps three dynamic arenas that together shaped the global discourse on peace: Cold War states, peace advocacy groups, and anticolonial liberationists. The thematic focus on peace moves transnationally where transnational discourses on peace emerged. It reveals the transnational networks that challenged and eventually undermined the Cold War order. It deterritorializes the Cold War by revealing the multiple divides that emerged within each Cold War camp, as peace activists challenged their own governments over the right path toward global peace, and also challenged each other over the best strategy. The Politics of Peace assumes a global perspective once peace advocates confronted the violence of national liberation movements in the Third World. It thus demonstrates that the Cold War was both more ubiquitous and less territorial than previously assumed.
Orbital mass in ANCA-associated vasculitides: data on clinical, biological, radiological and histological presentation, therapeutic management, and outcome from 59 patients
Authors: Durel Cécile-Audrey , Hot Arnaud , Trefond Ludovic , Aumaitre Olivier , Pugnet Gregory , Samson Maxime , Abad Sébastien , Belot Alexandre , Blanchard-Delaunay Claire , Cohen Pascal , Cohen-Aubard Fleur , Cottin Vincent , Crestani Bruno , Moreuil Claire De , Durupt Stéphane , Garzaro Margaux , Girszyn Nicolas , Godeau Bertrand , Hachulla Eric , Jamilloux Yvan , Jego Patrick , Killian Martin , Lazaro Estibaliz , Le Gallou Thomas , Liozon Eric , Martin Thierry , Papo Thomas , Perlat Antoinette , Pillet Pascal , Guillevin Loïc , Terrier Benjamin
Published: March 2019

Objective

Orbital mass is a rare and sight-threatening manifestation of ANCA-associated vasculitides, which remains a therapeutic challenge. We aimed to describe the presentation, therapeutic management and outcome of ANCA-associated vasculitides-related orbital mass.

Methods

We conducted a French nationwide retrospective study of patients with orbital mass in the setting of ANCA-associated vasculitides according to ACR criteria and/or Chapel Hill Consensus Conference definitions.

Results

Fifty-nine patients [33 women, median age 46 (range 7–90) years] were included. Fifty-six (95%) patients had granulomatosis with polyangiitis, two eosinophilic granulomatosis with polyangiitis and one microscopic polyangiitis. Orbital mass was unilateral in 47 (80%) cases, and seemed to develop from ENT involvement in most cases. Orbital mass biopsy was available in 32 (54%) patients, showing lymphoplasmacytic infiltration in 65%, fibrosis in 55%, granulomas in 48% and vasculitis in 36%. All patients but one received glucocorticoids as first-line therapy associated with immunosuppressive agents in 82%, mainly cyclophosphamide. Response to therapy was noted in 52% of patients treated with cyclophosphamide compared with 91% of those treated with rituximab. Twenty-seven (46%) patients required a second-line therapy because of relapse (59%) or refractory course (41%). Sequelae included visual impairment in 28%, with definitive blindness in 17%. Refractory course was associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.

Conclusion

Orbital mass is associated with refractory course and high frequency of sequelae, especially blindness. Refractory course is associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.
Toward perfect reads: short reads correction via mapping on compacted de Bruijn graphs
Authors: Limasset Antoine , Flot Jean-François , Peterlongo Pierre
Published: March 2019

Motivations

Short-read accuracy is important for downstream analyses such as genome assembly and hybrid long-read correction. Despite much work on short-read correction, present-day correctors either do not scale well on large data sets or consider reads as mere suites of k-mers, without taking into account their full-length read information.

Results

We propose a new method to correct short reads using de Bruijn graphs, and implement it as a tool called Bcool. As a first step, Bcool constructs a compacted de Bruijn graph from the reads. This graph is filtered on the basis ofk-mer abundance then of unitig abundance, thereby removing most sequencing errors. The cleaned graph is then used as a reference on which the reads are mapped to correct them. We show that this approach yields more accurate reads thank-mer-spectrum correctors while being scalable to human-size genomic datasets and beyond.

Availability and Implementation

The implementation is open source and available athttp://github.com/Malfoy/BCOOLunder the Affero GPL license and as a Bioconda package.

Contact

Antoine Limassetantoine.limasset@gmail.com& Jean-François Flotjflot@ulb.ac.be& Pierre Peterlongopierre.peterlongo@inria.fr
Spatial distribution and spread potential of sixteen Leptospira serovars in a subtropical region of Brazil
Authors: Jara Manuel , Escobar Luis E. , Rodriges Rogério O. , Frias Alba , Sanhueza Juan , Machado Gustavo
Published: March 2019

Leptospirosis is a bacterial disease that represents a major problem in animal and public health due to its high prevalence and widespread distribution. This zoonotic disease is most prevalent in tropical environments where conditions favor pathogen survival. The ecological preferences of Leptospira serovars are poorly understood, limiting our knowledge of where and when outbreaks can occur, which may result in misinformed prevention and control plans. While the disease can occur consistently in time and space in tropical regions, research on the ecology of Leptospirosis remains limited in subtropical regions. This research gap regarding Leptospira ecology brings public and veterinary health problems, impacting local economies. To fill this gap of knowledge, we propose to assess geographic and ecological features among Leptospira serovars in a subtropical area of Brazil where Leptospirosis is endemic to (i) highlight environmental conditions that facilitate or limit Leptospira spread and survival and (ii) reconstruct its geographical distribution. An ecological niche modeling framework was used to characterize and compare Leptospira serovars in both geographical and environmental space. Our results show that, despite the geographic overlap exhibited by the different serovars assessed, we found ecological divergence among their occupied ecological niches. Ecological divergences were expressed as ranges of potential distributions and environmental conditions found suitably by serovar, being Sejroe the most asymmetric. Most important predictors for the potential distribution of most serovars were soil pH (31.7%) and landscape temperature (24.2%). Identification of environmental preferences will allow epidemiologists to better infer the presence of a serovar based on the environmental characteristics of regions rather than inferences based solely on historical epidemiological records. Including geographic and ecological ranges of serovars also may help to forecast transmission potential of Leptospira in public health and the food animal practice.
The Genomic Ecosystem of Transposable Elements in Maize
Authors: Stitzer Michelle C. , Anderson Sarah N. , Springer Nathan M. , Ross-Ibarra Jeffrey
Published: March 2019

Transposable elements (TEs) constitute the majority of flowering plant DNA, reflecting their tremendous success in subverting, avoiding, and surviving the defenses of their host genomes to ensure their selfish replication. More than 85% of the sequence of the maize genome can be ascribed to past transposition, providing a major contribution to the structure of the genome. Evidence from individual loci has informed our understanding of how transposition has shaped the genome, and a number of individual TE insertions have been causally linked to dramatic phenotypic changes. But genome-wide analyses in maize and other taxa have frequently represented TEs as a relatively homogeneous class of fragmentary relics of past transposition, obscuring their evolutionary history and interaction with their host genome. Using an updated annotation of structurally intact TEs in the maize reference genome, we investigate the family-level ecological and evolutionary dynamics of TEs in maize. Integrating a variety of data, from descriptors of individual TEs like coding capacity, expression, and methylation, as well as similar features of the sequence they inserted into, we model the relationship between these attributes of the genomic environment and the survival of TE copies and families. Our analyses reveal a diversity of ecological strategies of TE families, each representing the evolution of a distinct ecological niche allowing survival of the TE family. In contrast to the wholesale relegation of all TEs to a single category of junk DNA, these differences generate a rich ecology of the genome, suggesting families of TEs that coexist in time and space compete and cooperate with each other. We conclude that while the impact of transposition is highly family- and context-dependent, a family-level understanding of the ecology of TEs in the genome can refine our ability to predict the role of TEs in generating genetic and phenotypic diversity.

‘Lumping our beautiful collection of transposons into a single category is a crime’

-Michael R. Freeling, Mar. 10, 2017
KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity
Authors: Turberfield Anne H. , Kondo Takashi , Nakayama Manabu , Koseki Yoko , King Hamish W. , Koseki Haruhiko , Klose Robert J.
Published: March 2019

CpG islands (CGI) are associated with the majority of mammalian gene promoters and function to recruit chromatin modifying enzymes. It has therefore been proposed that CGIs regulate gene expression through chromatin-based mechanisms, however in most cases this has not been directly tested. Here, we reveal that the histone H3 lysine 36 (H3K36) demethylase activity of the CGI-binding KDM2 proteins contributes only modestly to the H3K36me2-depleted state at CGI-associated gene promoters and is dispensable for normal gene expression. Instead, we discover that KDM2 proteins play a widespread and demethylase-independent role in constraining gene expression from CGI-associated gene promoters. We further show that KDM2 proteins shape RNA Polymerase II occupancy but not chromatin accessibility at CGI-associated promoters. Together this reveals a demethylase-independent role for KDM2 proteins in transcriptional repression and uncovers a new function for CGIs in constraining gene expression.