bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear transcriptomes at high resolution using retooled INTACT
Authors: Reynoso Mauricio A. , Pauluzzi Germain C. , Kajala Kaisa , Cabanlit Sean , Velasco Joel , Bazin Jérémie , Deal Roger , Sinha Neelima R. , Brady Siobhan M. , Bailey-Serres Julia
Published: August 2017

Isolated nuclei provide access to early steps in gene regulation involving chromatin as well as transcript production and processing. Here we describe transfer of the Isolation ofNuclei fromTAgged specificCellTypes (INTACT) to the monocot rice (Oryza sativaL.). The purification of biotinylated nuclei was redesigned by replacing the outer nuclear envelope-targeting domain of the Nuclear Tagging Fusion (NTF) protein with an outer nuclear envelope-anchored domain. This modified NTF was combined with codon optimizedE. coli BirAin a single T-DNA construct. We also developed inexpensive methods for INTACT, T-DNA insertion mapping and profiling of the complete nuclear transcriptome, including a rRNA degradation procedure that minimizes pre-rRNA transcripts. A high-resolution comparison of nuclear and steady-state poly (A)+transcript populations of seedling root tips confirmed the capture of pre-mRNA and exposed distinctions in diversity and abundance of the nuclear and total transcriptomes. This retooled INTACT can enable high-resolution monitoring of the nuclear transcriptome and chromatin in specific cell-types of rice and other species.

Improved technology and methodology for affinity purification of nuclei and analysis of nuclear transcriptomes, chromatin and other nuclear components.
Super-Resolution Microscopy Reveals Structural Mechanisms Driving the Nanoarchitecture of a Viral Chromatin Tether
Authors: Grant Margaret J. , Loftus Matthew S. , Stoja Aiola P. , Kedes Dean H. , Smith Malcolm Mitchell
Published: August 2017

By tethering their circular genomes (episomes) to host chromatin, DNA tumor viruses ensure retention and segregation of their genetic material during cell divisions. Despite functional genetic and crystallographic studies, there is little information addressing the three-dimensional structure of these tethers in cells, issues critical for understanding persistent infection by these viruses. Here, we have applied direct stochastic optical reconstruction microscopy (dSTORM) to establish the nanoarchitecture of tethers within cells latently infected with the oncogenic human pathogen, Kaposi's sarcoma-associated herpesvirus (KSHV). Each KSHV tether comprises a series of homodimers of the latency-associated nuclear antigen (LANA) that bind with their C-termini to the tandem array of episomal terminal repeats (TRs) and with their N-termini to host chromatin. Super-resolution imaging revealed that individual KSHV tethers possess similar overall dimensions and, in aggregate, fold to occupy the volume of a prolate ellipsoid. Using plasmids with increasing numbers of TRs, we found that tethers display polymer power-law scaling behavior with a scaling exponent characteristic of active chromatin. For plasmids containing a two-TR tether, we determined the size, separation, and relative orientation of two distinct clusters of bound LANA, each corresponding to a single TR. From these data, we have generated a three-dimensional model of the episomal half of the tether that integrates and extends previously established findings from epi-fluorescent, crystallographic, and epigenetic approaches. Our findings also validate the use of dSTORM in establishing novel structural insights into the physical basis of molecular connections linking host and pathogen genomes.
Preparation of H-Ras GTPase conjugated to lipid nanodiscs for NMR spectroscopy
Authors: Kovrigina Elizaveta A , Shah Sneha , Kovrigin Evgenii L
Published: August 2017

Ras GTPase is a peripheral membrane protein central to cellular signaling of growth and proliferation. Membrane attachment is critical for a range of Ras activities, therefore, ability to make faithfulin-vitrosamples of a mem-brane-bound Ras for detailed biophysical studies is a highly desirable goal. In this manuscript, we are describing preparation of a large-scale sample of isotopically labeled H-Ras conjugated to lipid nanodiscs. We demonstrate that the Ras-nanodisc sample is fairly stable to allow for a range of Nuclear Magnetic Resonance (NMR) and other biophysical measurements. The need to achieve a homogeneous protein-nanodisc ratio is also emphasized.
Somatic maintenance impacts the evolution of mutation rate
Authors: Rozhok Andrii , DeGregori James
Published: August 2017

The evolution of multi-cellular animals has produced a conspicuous trend toward increased body size. This trend has introduced at least two novel problems: an elevated risk of somatic disorders, such as cancer, and declining evolvability due to reduced population size, lower reproduction rate and extended generation time. Low population size is widely recognized to explain the high mutation rates in animals by limiting the presumed universally negative selection acting on mutation rates. Here, we present evidence from stochastic modeling that the direction and strength of selection acting on mutation rates is highly dependent on the evolution of somatic maintenance, and thus longevity, which modulates the cost of somatic mutations. We argue that this mechanism may have been critical in facilitating animal evolution.
Redistributive policies in decentralised systems: The effect of decentralisation on subnational social spending
Authors: KLEIDER HANNA
Published: August 2017

This article uses cross‐national data to examine the effects of fiscal and political decentralisation on subnational governments’ social expenditures. It revisits the benefit competition hypothesis put forward by fiscal federalism research, which posits that subnational governments in decentralised countries match welfare benefit reductions by their peers to keep taxes low and avoid an in‐migration of welfare dependents. As a consequence, subnational social expenditures are assumed to plateau at similar and low levels. Using a new cross‐national dataset on social expenditures in 334 subnational units across 14 countries and 21 years, the author explores whether benefit competition causes subnational governments to converge on similar levels of social spending. The analysis reveals that as countries decentralise, subnational social spending levels begin to diverge rather than converge, with some subnational governments reducing their social expenditures and others increasing them. Furthermore, decentralisation is not likely to be associated with lowest common denominator social policies, but with more variability in social expenditure. The article also examines the effects of other macro‐level institutions and demonstrates that policy coordination influences the relationship between decentralisation and subnational social spending levels.
Insect–plant–pathogen interactions as shaped by future climate: effects on biology, distribution, and implications for agriculture
Authors: Trębicki Piotr , Dáder Beatriz , Vassiliadis Simone , Fereres Alberto
Published: August 2017

Carbon dioxide (CO2) is the main anthropogenic gas which has drastically increased since the industrial revolution, and current concentrations are projected to double by the end of this century. As a consequence, elevated CO2 is expected to alter the earths’ climate, increase global temperatures and change weather patterns. This is likely to have both direct and indirect impacts on plants, insect pests, plant pathogens and their distribution, and is therefore problematic for the security of future food production. This review summarizes the latest findings and highlights current knowledge gaps regarding the influence of climate change on insect, plant and pathogen interactions with an emphasis on agriculture and food production. Direct effects of climate change, including increased CO2 concentration, temperature, patterns of rainfall and severe weather events that impact insects (namely vectors of plant pathogens) are discussed. Elevated CO2 and temperature, together with plant pathogen infection, can considerably change plant biochemistry and therefore plant defense responses. This can have substantial consequences on insect fecundity, feeding rates, survival, population size, and dispersal. Generally, changes in host plant quality due to elevated CO2 (e.g., carbon to nitrogen ratios in C3 plants) negatively affect insect pests. However, compensatory feeding, increased population size and distribution have also been reported for some agricultural insect pests. This underlines the importance of additional research on more targeted, individual insect–plant scenarios at specific locations to fully understand the impact of a changing climate on insect–plant–pathogen interactions.
High nymphal host density and mortality negatively impact parasitoid complex during an insect herbivore outbreak
Authors: Hall Aidan A. G. , Johnson Scott N. , Cook James M. , Riegler Markus
Published: August 2017

Insect herbivore outbreaks frequently occur and this may be due to factors that restrict top‐down control by parasitoids, for example, host–parasitoid asynchrony, hyperparasitization, resource limitation and climate. Few studies have examined host–parasitoid density relationships during an insect herbivore outbreak in a natural ecosystem with diverse parasitoids. We studied parasitization patterns of Cardiaspina psyllids during an outbreak in a Eucalyptus woodland. First, we established the trophic roles of the parasitoids through a species‐specific multiplex PCR approach on mummies from which parasitoids emerged. Then, we assessed host–parasitoid density relationships across three spatial scales (leaf, tree and site) over one year. We detected four endoparasitoid species of the family Encyrtidae (Hymenoptera); two primary parasitoid and one heteronomous hyperparasitoid Psyllaephagus species (the latter with female development as a primary parasitoid and male development as a hyperparasitoid), and the hyperparasitoid Coccidoctonus psyllae. Parasitoid development was host–synchronized, although synchrony between sites appeared constrained during winter (due to temperature differences). Parasitization was predominantly driven by one primary parasitoid species and was mostly inversely host‐density dependent across the spatial scales. Hyperparasitization by C. psyllae was psyllid‐density dependent at the site scale, however, this only impacted the rarer primary parasitoid. High larval parasitoid mortality due to density‐dependent nymphal psyllid mortality (a consequence of resource limitation) compounded by a summer heat wave was incorporated in the assessment and resulted in density independence of host–parasitoid relationships. As such, high larval parasitoid mortality during insect herbivore outbreaks may contribute to the absence of host density‐dependent parasitization during outbreak events.
Censoring and Distortion in the Hirschman–Herfindahl Index Computation
Authors: Naldi Maurizio , Flamini Marta
Published: August 2017

The Hirschman–Herfindahl Index (HHI) is a well known measure of market concentration. However, its exact computation would require the knowledge of the market share of all the companies. In this paper, accurate estimates of the HHI are computed even if just the market shares of the top companies are known (or just the top company and a few scattered ranked companies), by providing tight lower and upper bounds for the HHI. Similarly, when just the sales of the top companies are known, an upper bound is provided, which is the most relevant value if dominant positions have to be identified.
MiR‐155 inhibits proliferation and invasion by directly targeting PDCD4 in non‐small cell lung cancer
Authors: Liu Feng , Song Dalong , Wu Yanhu , Liu Xiang , Zhu Jinfu , Tang Yihu
Published: August 2017

Background

MicroRNAs are often abnormally expressed in human non‐small cell lung cancer (NSCLC) and are thought to play a critical role in the emergence or maintenance of NSCLC by binding to its target messenger RNA. We assessed the effects of miR‐155 on cell proliferation and invasion to elucidate the role played by miR‐155/PDCD4 in NSCLC.

Methods

Quantitative reverse transcription‐PCR, Western blotting, and cell counting kit‐8, luciferase, and transwell invasion assays were conducted on a normal human bronchial epithelial cell line (BEAS‐2B) and three NSCLC cell lines (SPC‐A‐1, A549, and H2170).

Results

We confirmed that miR‐155 was upregulated, while PDCD4 messenger RNA and protein levels were downregulated in NSCLC cell lines. miR‐155 negatively regulated PDCD4 at both transcriptional and post‐transcriptional levels. Moreover, PDCD4 was forecast as an assumed target of miR‐155 using bioinformatic methods and we demonstrated that PDCD4 was a direct target of miR‐155 using luciferase reporter assays. Furthermore, PDCD4 overexpression could restrain NSCLC proliferation and invasion induced by miR‐155.

Conclusion

Our results collectively demonstrate that miR‐155 exerts an oncogenic role in NSCLC by directly targeting PDCD4.
Climate warming effects on grape and grapevine moth (Lobesia botrana) in thePalearcticregion
Authors: Gutierrez Andrew Paul , Ponti Luigi , Gilioli Gianni , Baumgärtner Johann
Published: August 2017

The grapevine mothLobesia botrana(Den. & Schiff.) (Lepidoptera: Tortricidae) is the principal native pest of grape in thePalearctic region. In the present study, we assessed prospectively the relative abundance of the moth inEurope and theMediterraneanBasin using linked physiologically‐based demographic models for grape andL. botrana. The model includes the effects of temperature, day‐length and fruit stage on moth development rates, survival and fecundity.

Daily weather data for 1980–2010 were used to simulate the dynamics of grapevine andL. botranain 4506 lattice cells across the region. Average grape yield and pupae per vine were used as metrics of favourability. The results were mapped using thegrassGeographic Information System (http://grass.osgeo.org).

The model predicts a wide distribution forL. botranawith highest populations in warmer regions in a wide band along latitude 40°N.

The effects of climate warming on grapevine andL. botranawere explored using regional climate model projections based on theA1Bscenario of an average +1.8 °C warming during the period 2040–2050 compared with the base period (1960–1970). Under climate change, grape yields increase northwards and with a higher elevation but decrease in hotter areas. Similarly,L. botranalevels increase in northern areas but decrease in the hot areas where summer temperatures approach its upper thermal limit.
Keep Burning Coal or the Manatee Gets It: Rendering the Carbon Economy Invisible through Endangered Species Protection
Authors: Carr John , Milstein Tema
Published: August 2017

As ever expanding accretions of human industrial and residential development pave over endangered Florida manatees’ warm water springs winter habitat, more than half of the manatees have come to depend upon fossil fuel‐burning power plant hot water effluent channels for survival. In an effort to save these manatees, environmental activists have leveraged the US Endangered Species Act to protect the effluent streams and, by extension, have enshrined the power plants themselves as ecological saviors. This study interrogates the paradoxes within the resulting spatio‐legal regime. Recognizing the problematic human/nature binary at the heart of dominant Western practices, our study suggests spatial and legal regimes do not simply reify and reproduce this binary but also produce invisible ecocultural spaces that are essential to prop up an inherently unstable, illusory, and ultimately destructive definition of human existence.
Understanding Epigenetic Effects of Endocrine Disrupting Chemicals: From Mechanisms to Novel Test Methods
Authors: Alavian‐Ghavanini Ali , Rüegg Joëlle
Published: August 2017

Endocrine‐disrupting chemicals (EDCs) are man‐made chemicals that interfere with hormonal signalling pathways. They are used in, for example, production of common household materials, in resin‐based medical supplies and in pesticides. Thus, they are environmentally ubiquitous and human beings and wildlife are exposed to them on a daily basis. Early‐life exposure to EDCs has been associated with later‐life adversities such as obesity, diabetes and cancer. Mechanisms underlying such associations are unknown but are likely to be mediated by epigenetic changes induced by EDCs. Epigenetics is the study of changes in gene function that are heritable but do not entail a change in DNA sequence. EDCs have been shown to affect epigenetic marks such as DNA methylation and histone modifications. The scope of this article was to review today's knowledge about mechanisms involved in EDC‐induced epigenetic changes and to discuss how this knowledge could be used for designing novel methods addressing epigenetic effects of EDCs.
Clinical and social characteristics associated with reduced visual acuity at presentation in Australian patients with neovascular age‐related macular degeneration: a prospective study from a long‐term observational data set. The Fight Retinal Blindness! Project
Authors: Nguyen Vuong , Daien Vincent , Guymer Robyn H , McAllister Ian L , Morlet Nigel , Barthelmes Daniel , Gillies Mark C
Published: August 2017

Importance

Identifying variables that influence presenting visual acuity (VA) in patients with neovascular age‐related macular degeneration (nAMD) is important because it is a strong predictor of long‐term outcomes.

Background

To assess the clinical and social characteristics associated with low presenting VA in nAMD patients.

Design

The present study is a cross‐sectional analysis from a prospective, observational database.

Participants

We identified 3242 treatment‐naïve patients from 54 Australian practices in the Fight Retinal Blindness! registry.

Methods

Age, gender, ethnicity and VA were recorded at the baseline visit. Socio‐economic status was determined using the Australian Bureau of Statistics socio‐economic indexes for areas.

Main Outcome Measures

Association between clinical and socio‐economic characteristics with presenting VA was identified.

Results

Poor VA (≤35 letters) in the presenting eye was associated with older age (adjusted odds ratio [AOR]: 1.33 for patients aged ≥80 years vs. <80 years [95% confidence interval, CI: 1.04, 1.71]), treatment at a public practice (AOR: 1.91 for public vs. private practices [95% CI: 1.46, 2.50]) and intermediate (36–69 letters) VA in the fellow eye (AOR: 0.67 [95% CI: 0.47, 0.95] and 0.64 [95% CI: 0.48, 0.85] for poor [≤35 letters] and good [≥70 letters] VA vs. intermediate VA in the fellow eye). Gender, ethnicity and socio‐economic status were not independently associated with VA at presentation.

Conclusions and Relevance

Poor presenting vision is detrimental to the long‐term outcomes of nAMD. Poor presentation of nAMD in Australia may not be related to socio‐economic circumstances, but due to systems of care. Further research is warranted to determine why patients at public practices present with worse vision compared with private practices in Australia.
Risk factors of age‐related cataract in a Chinese adult population: the Taizhou Eye Study
Authors: Tang Yating , Wang Xiaofeng , Wang Jiucun , Jin Li , Huang Wei , Luo Yi , Lu Yi
Published: August 2017

Importance

Cataract risk factors data will provide epidemic evidence for cataract prevention.

Background

This study aimed to study the risk factors for age‐related cataract in a Chinese adult population.

Design

This is a population‐based, cross‐sectional study.

Participants

A total of 10 234 eligible subjects ≥45 years old (response rate: 78.1%) were included in the study.

Methods

We conducted detailed eye examinations including presenting visual acuity, best‐corrected visual acuity, slit lamp examination of lens opacities and fundus examination. Questionnaires about lifestyle were administered. Measurements of blood pressure, heart rate and body mass index were collected. Serological metabolic indicators, including fasting blood glucose, triglycerides, cholesterol, lipoprotein, were also evaluated. We used stepwise multivariate logistic regression model to evaluate the association of these risk factors with any cataract and subtypes of cataract.

Main Outcome Measures

Odds ratios of risk factors for cataract were calculated.

Results

For any cataract, we found age, gender (female), increased outdoor activity, no outdoor eye protection, high myopia, high low‐density lipoprotein, low high‐density lipoprotein, lower education level and increased pickled food intake were independent risk factors. When further examined the risk factors of different subtypes of cataract, we found that these risk factors also existed, but there were slight differences among different subtypes. In addition, for cortical cataract, lower annual family income and high diastolic pressure were additional independent risk factors.

Conclusions and Relevance

Reduced outdoor activity, outdoor eye protection, prevention of high myopia, higher education level, controlled blood pressure, improved high‐density lipoprotein and low‐density lipoprotein levels and reduced pickled food intake may help to reduce the risk of age‐related cataract development.
The impact of pediatric obesity on hospitalized children with lower respiratory tract infections in the United States
Authors: Okubo Yusuke , Nochioka Kotaro , Testa Marcia A.
Published: August 2017

Objective

Obesity is the most common public health problem and is a clinically complicating risk factor among hospitalized children. The impact of pediatric obesity on the severity and morbidity of lower respiratory tract infections remains unclear.

Materials and Methods

We conducted a retrospective cohort study of bronchitis and pneumonia among children aged 2‐20 years using hospital discharge records. The data were obtained from the Kid's Inpatient Database in 2003, 2006, 2009, and 2012, and were weighted to estimate the number of hospitalizations in the United States. We used the International Classification of Diseases, Ninth Revision, Clinical Modification code (278.0×) to classify whether the patient was obese or not. We investigated the associations between pediatric obesity and use of mechanical ventilation using multivariable logistic regression model. In addition, we ascertained the relationships between pediatric obesity, comorbid blood stream infections, mean healthcare cost, and length of hospital stay.

Results

We estimated a total of 133 602 hospitalizations with pneumonia and bronchitis among children aged between 2 and 20 years. Obesity was significantly associated with use of mechanical ventilation (adjusted OR 2.90, 95% CI 2.15‐3.90), comorbid bacteremia or septicemia (adjusted OR 1.58, 95% CI 1.03‐2.44), elevated healthcare costs (adjusted difference $383, 95%CI $276‐$476), and prolonged length of hospital stay (difference 0.32 days, 95%CI 0.23‐0.40 days), after adjusting for patient and hospital characteristics using multivariable logistic regression models.

Conclusions

Pediatric obesity is an independent risk factor for severity and morbidity among pediatric patients with lower respiratory tract infections. These findings suggest the importance of obesity prevention for pediatric populations.
Anxiety and depression in adult outpatients with bronchiectasis: Associations with disease severity and health‐related quality of life
Authors: Gao Yong‐Hua , Guan Wei‐Jie , Zhu Ya‐Nan , Chen Rong‐Chang , Zhang Guo‐Jun
Published: August 2017

Background

Anxiety and depression might frequently affect bronchiectasis patients, but data in Chinese patients, including their association with disease severity assessed with Bronchiectasis Severity Index (BSI) and FACED score, are limited.

Objective

To investigate the rate, risk factors, association with disease severity and impact of anxiety and depression on health‐related quality of life (HRQoL) in adult outpatients with steady‐state bronchiectasis.

Methods

This cross‐sectional study included 163 outpatients (102 females; mean age, 45.8 years) and 80 healthy subjects (47 females; mean age, 47.1 years). Demographic, clinical indices, radiology, spirometry, aetiology, sputum bacteriology, Hospital Anxiety and Depression Scales (HADS), Pittsburgh Sleep Quality Index (PSQI) and St. George's Respiratory Questionnaire (SGRQ) were assessed.

Results

Patients with steady‐state bronchiectasis had a higher rate of depression (HADS‐depression >7) (30.1% vs 10.0%, P = .001) and anxiety (HADS‐anxiety >7; 39.9% vs 6.3%, P < .001) compared with healthy subjects. Notably, no significant differences in the rate of anxiety and depression were found across different disease severity, assessed with BSI and FACED score (all P > .05). In multivariate model, factors associated with anxiety included younger age (OR = 1.05), education below college graduate (OR = 4.55) and sleep disturbance (PSQI ≥ 6; OR = 2.95); whereas sleep disturbance was the sole factor associated with depression (OR = 5.98). Patients with either depression or anxiety had more markedly impaired HRQoL affecting most domains than those without.

Conclusions

Anxiety and depression are common in bronchiectasis and can negatively affect HRQoL, but not related to disease severity. Prompt assessment and treatment of these mental disorders, regardless of bronchiectasis severity, are advocated and might improve HRQoL.
Pleuroparenchymal fibroelastosis in heterogeneous clinical conditions: Clinicopathologic analysis of 7 cases
Authors: Cha Yoon Jin , Han Joungho , Chung Man Pyo , Kim Tae Jung , Shin Sumin
Published: August 2017

Background and Aims

Pleuroparenchymal fibroelastosis (PPFE) is classified as a rare idiopathic interstitial pneumonia, and its clinicopathologic features remain unclear. We sought to investigate the clinical, radiologic, and pathologic features of patients with histologically proven PPFE.

Methods

Seven patients who had histologic features of PPFE that were definitive or consistent with PPFE were included. Clinical data and radiologic findings of chest computed tomography were obtained. Histologic evaluation was performed by 2 pathologists.

Results

Four patients had elevated serum autoantibodies, 3 had a history of organ transplantation, and 1 had acute Aspergillus infection. All patients had various degrees of restrictive patterns on pulmonary function tests. Histologic examination revealed a variable extent of PPFE. Fibroblastic foci, patchy lymphocytic infiltration, and pneumothorax were observed, but these findings were nonspecific. Radiologically, PPFE lesions were distributed diffusely, rather than being limited to the upper lungs.

Conclusions

PPFE seems to be a histologic finding that may partly overlap with other chronic lung diseases. There can be various underlying clinical states.
Contracting out of basic health facilities in Pakistan: Are the lessons generalizable?
Authors: Bano Masooda
Published: August 2017

Amid growing support within international development agencies for the privatization of health facilities in developing countries, contracting out of the Basic Health Units (BHUs) in Pakistan has been presented as a success. This article argues for caution in generalizing results from this model. It shows that the model improved service delivery because the organization taking over the BHUs was itself a government‐owned QUANGO (Quasi‐Autonomous NGO); similar concessions would not have been granted to a private provider. Further, the article shows that, given the strong resistance that the model continues to receive from administrators within the state system, development agencies must consider whether models that try to sidestep the bureaucracy instead of working towards installing good practice within the state system, can be viewed as a success.
Plant water stress and previous herbivore damage affect insect performance
Authors: HAHN PHILIP G. , MARON JOHN L.
Published: August 2017

1. Short‐term changes in plant resistance traits can be affected by abiotic factors or damage by herbivores, although how the combined effects of abiotic factors and previous damage affect subsequent insect larval development is not well understood.

2. Complementary glasshouse and field experiments were conducted to evaluate whether plant water stress and previous herbivore damage influenced monarch (Danaus plexippus) larval development on common milkweed, Asclepias syriaca.

3. In the glasshouse, water stress altered a suite of A. syriaca functional traits but did not affect nutrient content, whereas herbivore damage increased leaf nitrogen (N) and reduced the carbon:nitrogen (C:N) ratio. A bioassay experiment showed that monarch larval survival was lower on well‐watered plants that were previously damaged by monarch larva than on damaged and drought‐stressed plants. Bioassay larvae consumed less leaf tissue of previously damaged plants, whereas monarch larval mass was affected additively by water stress and previous damage, after correcting for the amount of leaf tissue consumed.

4. In a 2‐year field experiment, monarch larval performance was higher on previously damaged A. syriaca plants that received experimentally reduced rainfall, relative to plants receiving ambient rainfall.

5. Collectively, these results from glasshouse and field experiments suggest that insect performance was highest on previously damaged plants under water stress and highlight the additive and interactive roles of abiotic and biotic factors on herbivore performance.
Novel Therapeutic Targets Against Spreading Depression
Authors: Chen Shih‐Pin , Ayata Cenk
Published: August 2017

Migraine is among the most prevalent and disabling neurological diseases in the world. Cortical spreading depression (SD) is an intense wave of neuronal and glial depolarization underlying migraine aura, and a headache trigger, which has been used as an experimental platform for drug screening in migraine. Here, we provide an overview of novel therapeutic targets that show promise to suppress SD, such as acid‐sensing ion channels, casein kinase Iδ, P2X7‐pannexin 1 complex, and neuromodulation, and outline the experimental models and essential quality measures for rigorous and reproducible efficacy testing.
Migraine Prophylaxis and Acute Treatment Patterns Among Commercially Insured Patients in the United States
Authors: Woolley J. Michael , Bonafede Machaon M. , Maiese Brett A. , Lenz Robert A.
Published: August 2017

Objectives

To describe prophylactic and acute medication treatment patterns, including timing, medication type, and duration of use in migraine patients initiating prophylaxis.

Background

Patients with migraine can be treated with acute and prophylactic therapies. Current treatment options for migraine prophylaxis are associated with poor tolerability and low adherence and persistence.

Methods

This retrospective cohort study used the Truven Health Analytics MarketScan® Research Databases to identify adults in the United States with a migraine diagnosis who initiated migraine prophylactic medication (index event) between January 1, 2008, and December 31, 2011. Prescribed prophylactic medications evaluated included topiramate, beta‐blockers, and tricyclic antidepressants. Patients were required to have 12 months of pre‐ and post‐index continuous enrollment. Patient characteristics, migraine‐specific prescribed prophylactic treatment patterns (including gaps in therapy, treatment switches, and additions of index medications), and prescribed acute medication utilization were assessed.

Results

The study population comprised 107,122 patients, with 52,275 (49%) initiating topiramate, 22,658 (21%) initiating beta‐blockers, and 32,189 (30%) initiating tricyclic antidepressants. Mean (SD) age was 41 (12) years and 83% were female. Persistence with migraine prophylactic medication was low; 81% of patients had gaps of >90 days in their migraine prophylaxis in the first year. The gap in therapy occurred early in treatment (mean, 95 days), and only 10% of patients restarted prophylactic therapy within that year. Switching from index medication to another prophylactic medication or adding prophylaxis was uncommon (13% and 5%, respectively). One year after initiating prophylaxis, 65% of patients were not receiving any prophylactic therapies. Most patients initiating migraine prophylaxis also utilized acute treatments (81%); opioid use was more frequent than triptan use (53% vs 48%) and was common (40%) among patients without other chronic pain conditions (eg, arthritis, fibromyalgia, and lower back pain).

Conclusion

Patients with migraine who initiated prophylactic therapy had poor persistence with early gaps in therapy, were unlikely to switch prophylactic treatments, and most discontinued prophylaxis by the end of the first year.
Economics of Inhaled Oxygen Use as an Acute Therapy for Cluster Headache in the United States of America
Authors: O'Brien Megan , Ford Janet H. , Aurora Sheena K. , Govindan Sriram , Tepper Deborah E. , Tepper Stewart J.
Published: August 2017

Background

Cluster headache (CH) is a primary headache disorder associated with low levels of diagnosis and high unmet medical need. The pain attacks, associated anxiety, and fear in anticipation of the attacks are extremely debilitating to a patient with CH. For acute therapy, treatment guidelines recommend inhalation of high flow oxygen during the period of an attack. However, the use of oxygen for treatment of CH remains largely underutilized.

Objectives

The objectives of the study, which covered each of the US states, were to map the current market landscape of medical grade oxygen for use in CH and to develop a cost simulator based on a patient's needs and geography.

Methods

Desk research was undertaken to obtain price lists and product catalogs from wholesale and retail suppliers of medical grade oxygen across all US states. Base case scenarios for chronic and episodic forms of CH were assumed. A cost simulator was used to calculate the cost of oxygen use using inputs including the state in USA, tank size and price, exacerbations per year, duration of exacerbation, attacks per day, flow rate and duration of flow. Information was also collected to determine if healthcare insurers covered the costs of home oxygen use for CH.

Results

Out of the 42 US states where pricing information of medical grade oxygen was available from suppliers, in 38 states the annual cost of high‐flow oxygen for a patient with episodic CH was estimated to be <$1000. In 39 states, the annual cost of high‐flow oxygen for a patient with chronic CH was estimated to be <$5000. Most of the home oxygen suppliers were familiar with CH and stocked the special non‐rebreather masks and regulators necessary for this condition. It was found that many of the private commercial healthcare insurance providers reimbursed the cost of oxygen use for CH. However, the US Centers for Medicare and Medicaid Services (CMS) maintains there is insufficient evidence for coverage and continues to deny coverage for US Medicare and Medicaid patients.

Conclusions

Results from our study showed that the current costs for oxygen use as an acute therapy in CH are not prohibitively expensive for patients and healthcare insurance providers. Apart from CMS, many insurers do reimburse the cost of oxygen use for CH. Our study suggests that further research is needed to determine if a lack of physician awareness about treatments and ways to prescribe are barriers for patients to access the high‐flow oxygen treatment.
Dl‐3‐n‐butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4/NF‐κB signalling
Authors: He Zili , Zhou Yulong , Lin Li , Wang Qingqing , Khor Sinan , Mao Yuqin , Li Jiawei , Zhen Zengming , Chen Jian , Gao Zhenzhen , Wu Fenzan , Zhang Xie , Zhang Hongyu , Xu Hua‐Zi , Wang Zhouguang , Xiao Jian
Published: August 2017

In this study, we examined the neuroprotective effects and anti‐inflammatory properties of Dl‐3‐n‐butylphthalide (NBP) in Sprague‐Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL‐positive cells at 7 days post‐injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF‐κB expression at 1 day post‐injury. In a co‐culture system with BV‐2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV‐2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV‐2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF‐κB expression in BV‐2 cells. Our findings demonstrate that NBP may have neuroprotective and anti‐inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF‐κB signalling.
Risk prediction of post‐hepatectomy liver failure in patients with perihilar cholangiocarcinoma
Authors: Lee Eung Chang , Park Sang‐Jae , Han Sung‐Sik , Shim Jae Ryong , Park Hyeong Min , Lee Seung Duk , Kim Seong Hoon
Published: August 2017

Background and Aim

In most patients with perihilar cholangiocarcinoma (PHCC), major hepatectomy and extrahepatic bile duct resection are needed for surgical radicality, and a high risk of hepatic insufficiency exists. This study aims to develop a prediction model for post‐hepatectomy liver failure (PHLF) in patients with PHCC.

Methods

A total of 143 patients who underwent major liver resection and extrahepatic bile duct resection for PHCC between October 2001 and December 2013 were included. Clinically relevant PHLF was defined as liver failure corresponding to grade B or C of the International Study Group of Liver Surgery criteria. Multivariate logistic regression was used to develop the PHLF risk model. Model performance was evaluated internally using the area under the curve analysis (discrimination) after 1000 bootstrap resampling and the Hosmer–Lemeshow goodness‐of‐fit test (calibration).

Results

Post‐hepatectomy liver failure occurred in 43.4% of patients (n = 62). In multivariate analysis, PHLF was significantly associated with future liver remnant ratio (odds ratio [OR] per 10% = 0.68, 95% confidence interval [CI] 0.51–0.88), intraoperative blood loss (OR per 1 L = 1.82, 95% CI 1.11–3.17), and preoperative prothrombin time > 1.20 (OR = 3.22, 95% CI 1.15–9.97). The PHLF risk score model showed good discrimination (area under the curve = 0.708, 95% CI 0.623–0.793) and calibration (P = 0.227).

Conclusions

The risk model proposed in this study accurately predicted PHLF in patients with PHCC. This offers surgeons a practical guide to quantitative risk assessment of hepatic insufficiency and aids decision‐making in surgical treatment and perioperative management.
Environmental and Economic Implications of Distributed Additive Manufacturing: The Case of Injection Mold Tooling
Authors: Huang Runze , Riddle Matthew E. , Graziano Diane , Das Sujit , Nimbalkar Sachin , Cresko Joe , Masanet Eric
Published: August 2017

Additive manufacturing (AM) holds great potentials in enabling superior engineering functionality, streamlining supply chains, and reducing life cycle impacts compared to conventional manufacturing (CM). This study estimates the net changes in supply‐chain lead time, life cycle primary energy consumption, greenhouse gas (GHG) emissions, and life cycle costs (LCC) associated with AM technologies for the case of injection molding, to shed light on the environmental and economic advantages of a shift from international or onshore CM to AM in the United States. A systems modeling framework is developed, with integrations of lead‐time analysis, life cycle inventory analysis, LCC model, and scenarios considering design differences, supply‐chain options, productions, maintenance, and AM technological developments. AM yields a reduction potential of 3% to 5% primary energy, 4% to 7% GHG emissions, 12% to 60% lead time, and 15% to 35% cost over 1 million cycles of the injection molding production depending on the AM technology advancement in future. The economic advantages indicate the significant role of AM technology in raising global manufacturing competitiveness of local producers, while the relatively small environmental benefits highlight the necessity of considering trade‐offs and balance techniques between environmental and economic performances when AM is adopted in the tooling industry. The results also help pinpoint the technological innovations in AM that could lead to broader benefits in future.
The Influence of State‐Ownership on Eco‐Innovations in Russian Manufacturing Firms
Authors: Roud Vitaliy , Thurner Thomas Wolfgang
Published: August 2017

This paper studies drivers for eco‐innovation in Russian manufacturing firms on a sample of 2,212 innovative firms, of which over 600 introduced eco‐innovations. The companies in our sample specifically mention environmental regulation as a reason for engaging in eco‐innovations. Furthermore, we show that those firms who engage in eco‐innovations are motivated even stronger by the desire to increase resource efficiency. Companies under state ownership are especially prone to a higher likelihood to invest. We conclude that regulations are mostly relevant to the late comers who are obliged to follow minimum standards. On the other hand, the state uses its controlling influence to press companies under their control to exceed these minimum standards. Thus, we argue, state ownership does indeed have an influence on both the likelihood to eco‐innovate and on the levels of spending. Eco‐innovative state‐owned companies are only prone to invest in eco‐innovations, if they get additional money.
Closing the Loop on E‐waste: A Multidisciplinary Perspective
Authors: Bridgens Ben , Hobson Kersty , Lilley Debra , Lee Jacquetta , Scott Janet L. , Wilson Garrath T.
Published: August 2017

This paper describes the challenges faced, and opportunities identified, by a multidisciplinary team of researchers developing a novel closed loop system to recover valuable metals and reduce e‐waste, focusing on mobile phones as a case study. This multidisciplinary approach is contrasted with current top‐down approaches to making the transition to the circular economy (CE). The aim of the research presented here is to develop a product service system (PSS) that facilitates the recovery of valuable functional components and metals from mobile phone circuit boards. To create a holistic solution and limit unintended consequences, in addition to technological solutions, this paper considers appropriate component lifetimes; the (often ignored) role of the citizen in the circular economy; customer interaction with the PSS; environmental life cycle assessment; and social impacts of the proposed PSS. Development of enabling technologies and materials to facilitate recovery of components and metals and to provide an emotionally durable external enclosure is described. This research also highlights the importance of understanding value in the CE from a multifaceted and interdisciplinary perspective.
Land Use Change in India (1700–2000) as Examined through the Lens of Human Appropriation of Net Primary Productivity
Authors: deSouza Priyanka , Malhi Yadvinder
Published: August 2017

Land use caused by human socioeconomic activities is a driver of change in the global environment. To understand and quantify land‐use change on Earth's natural systems, interdisciplinary approaches linking biophysical and socioeconomic parameters are required. One approach to understand the degree of terrestrial colonization of the biosphere is using the human appropriation of net primary productivity (HANPP). HANPP is defined as the difference between the net primary productivity (NPP) of potential vegetation and the actual NPP for a given area of land. Here, we use HANPP as a lens to examine land‐use change in India from 1700 to 2007 using a spatially explicit data set that extends over this period. We also used the nongridded, Food and Agriculture Organization (FAO) data set to calculate HANPP for India from 1961 to 2012 and compared our results. The average potential NPP for India was estimated to be 664 grams of carbon per square meter per year (g C/m2/year). Between 1700 and 2012, the fraction of pastureland and cropland increased from 20% to almost 60%. HANPP as a fraction of the potential NPP increased from 29% to 73% over this period. Calculations of HANPP using the FAO data set yielded an increase from 600 g C/m2 to just over 700 g C/m2 between 1961 and 2012. We also calculated the embodied HANPP of India by considering imports and exports, but the difference between the two is negligible in comparison to the HANPP of India. We further examined the variation of HANPP with socioeconomic parameters such as the Human Development Index (HDI) and population density. There was a roughly negative trend of HANPP with HDI. HANPP roughly increases with population density and then plateaus above a population density of roughly 200 persons per square kilometer.
Life Cycle Inventory Analysis of the Wood Pallet Repair Process in the United States
Authors: Park Jonghun , Horvath Laszlo , Bush Robert J.
Published: August 2017

This study developed gate‐to‐gate life cycle inventory (LCI) data for the repair of 48 by 40 inch (1,219 by 1,016 millimeter [mm]) stringer‐class wood pallets in the United States. Data were collected from seven wood pallet repair facilities. Approximately 1.98 FBM (foot, board measure) (4.67E‐03 cubic meters) of lumber were used for repairing each 48 by 40 inch (1,219 by 1,016 mm) stringer‐class wood pallet, the majority (97%) recovered from damaged pallets received by the pallet repair facilities. Repair equipment powered by electricity made the largest contribution to greenhouse gas (GHG) emissions. Steel nails used for the pallet repair had the largest contribution to GHG emissions among the material inputs, while use of recovered lumber yielded the largest GHG emissions credits. Overall, the repair process for a 48 by 40 inch (1,219 by 1,016 mm) stringer‐class wood pallet had GHG credits rather than a positive GHG emission due to the GHG offsets from co‐products.
NaMYB8 regulates distinct, optimally distributed herbivore defense traits
Authors: Schäfer Martin , Brütting Christoph , Xu Shuqing , Ling Zhihao , Steppuhn Anke , Baldwin Ian T. , Schuman Meredith C.
Published: August 2017

When herbivores attack, plants specifically reconfigure their metabolism. Herbivory on the wild tobacco Nicotiana attenuata strongly induces the R2R3 MYB transcriptional activator MYB8, which was reported to specifically regulate the accumulation of phenolamides (PAs). We discovered that transcriptional regulation of trypsin protease inhibitors (TPIs) and a threonine deaminase (TD) also depend on MYB8 expression. Induced distributions of PAs, TD and TPIs all meet predictions of optimal defense theory: their leaf concentrations increase with the fitness value and the probability of attack of the tissue. Therefore, we suggest that these defensive compounds have evolved to be co‐regulated by MYB8.