bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid assembly of the genome of the entomopathogenic nematodeSteinernema carpocapsaeidentifies the X-chromosome
Authors: Serra Lorrayne , Macchietto Marissa , Macias-Muñoz Aide , McGill Cassandra Joan , Rodriguez Isaryhia Maya , Rodriguez Bryan , Murad Rabi , Mortazavi Ali
Published: March 2019

Entomopathogenic nematodes from the genusSteinernemaare lethal insect parasites that quickly kill their insect hosts with the help of their symbiotic bacteria.Steinernema carpocapsaeis one of the most studied entomopathogens due to its broad lethality to diverse insect species and its effective commercial use as a biological control agent for insect pests, as well as a genetic model for studying parasitism, pathogenesis, and symbiosis. In this study, we used long-reads from the Pacific Biosciences platform and BioNano Genomics Irys system to assemble the best genome ofS. carpocapsaeALL strain to date, comprising 84.5 Mb in 16 scaffolds, with an N50 of 7.36Mb. The largest scaffold, with 20.9Mb, was identified as chromosome X based on sex-specific genome sequencing. The high level of contiguity allowed us to characterize gene density, repeat content, and GC content. RNA-seq data from 17 developmental stages, spanning from embryo to adult, were used to predict 30,957 gene models. Using this new genome, we performed a macrosyntenic analysis toCaenorhabditis elegansandPristionchus pacificusand foundS. carpocapsae’schromosome X to be primarily orthologous toC. elegans’andP. pacificus’chromosome II and IV. We also investigated the expansion of protein families and gene expression differences between male and female stage nematodes. This new genome and more accurate set of annotations provide a foundation for new comparative genomic and gene expression studies within theSteinernemaclade and across the Nematoda phylum.

Article Summary

The insect killing worms Steinernema carpocapsae is a model organism for parasitism and symbiosis. The authors have used long reads and optical mapping to generate substantially contiguous assembly and a new set of gene annotations. They have identified the X chromosome as well as expansions in specific family proteases found in the venom of this worm. A macrosyntenic analysis withC. elegansshows a broad conservation of ancestral chromosomes with the exception of chromosome X. This new assembly will be useful to theSteinernemacommunity and the broader nematode genomics community.
Fenestrae-associated protein Plvap regulates the rate of blood-borne proteins passage into the hypophysis
Authors: Gordon Ludmila , Blechman Janna , Shimoni Eyal , Gur Dvir , Anand-Apte Bela , Levkowitz Gil
Published: March 2019

To maintain body homeostasis, endocrine systems must detect and integrate a multitude of blood-borne peripheral signals. This is mediated by specialized permeable pores in the endothelial membrane, dubbed fenestrae. Plasmalemma vesicles-associated protein (Plvap) is located in the fenestral diaphragm and is thought play a role in the selective passage of proteins through the fenestrae. However, this suggested function has yet to be demonstrated directly. Here, we studied the development of fenestrated capillaries in a major neuroendocrine interface between the blood and brain, namely the hypophysis. Using a transgenic permeability biosensor to visualize the vascular excretion of a genetically tagged plasma protein (DBP-EGFP), we show that the developmental acquisition of vascular permeability is associated with differential expression of zebrafish plvap orthologs in the hypophysis versus brain. Ultrastructural analysis of the hypophyseal vasculature revealed that plvapb mutants display deficiencies in fenestral and stomatal diaphragms as well as increased density of fenestrae, but not of caveolae. Measurements of DBP-EGFP dynamics in live plvapb mutant larvae provided a direct proof that Plvap limits the rate of blood-borne protein passage through fenestrated endothelia. Overall, we present the regulatory role of Plvap in the development of blood-borne protein detection machinery in a major neuroendocrine interface between the brain and the general circulation.
Autologous adipose-derived stem cell transplantation enhances healing of wound with exposed bone in a rat model
Authors: Hamada Tomo , Matsubara Hidenori , Yoshida Yasuhisa , Ugaji Shuhei , Nomura Issei , suchiya Hiroyuki T
Published: March 2019

Objectives

Soft tissue wounds with exposed bone often require extended healing times and can be associated with severe complications. We describe the ability of artificial dermis with autogenic adipose-derived stem cells (ADSCs) to promote the healing of wounds with exposed bone in a rat model.

Methods

Adipose tissues harvested from the bilateral inguinal regions of Wistar rats were used as ADSCs. Rats were randomly divided into control and ADSC groups to investigate the efficacy of ADSC transplantation for wound healing (n=20 per group). Soft tissue defects were created on the heads of the rats and were covered with artificial dermis with or without the seeded ADSCs. Specimens from these rats were evaluated using digital image analysis, histology, immunohistochemistry, cell labeling, and real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR).

Results

The average global wound area was significantly smaller in the ADSC group than in the control group on days 3, 7, and 14 after surgery (p<0.05). After 14 days, the blood vessel density in the wound increased by 1.6-fold in the ADSC group compared with that in the control group (p<0.01). Real-time RT-PCR results showed higherFgfbandVegfexpression levels at all time points, and higherTgfb1andTgfb3expression levels until 14 days after surgery, in the ADSC group than in the control group (p<0.05).

Conclusions

In wounds with exposed bone, autogenic ADSCs can promote vascularization and wound healing. Use of this cell source has multiple benefits, including convenient clinical application and lack of ethical concerns.
Effect of topical soluble epoxide hydrolase inhibition in a preclinical diabetic wound healing model
Authors: Reisdorf William C. , Rajpal Neetu , Gehman Andrew J. , Jain Piyush , Burgert Mark E. , Sonti Sujatha , Agarwal Pankaj , Rajpal Deepak K.
Published: March 2019

The objective of this study was to test a topical formulation of EPHX2 inhibitor, GSK2256294, in a dermal wound diabetic (db/db) mouse model. Comparisons were made between groups treated with EPHX2 inhibitor, matching vehicle control and a currently approved treatment for diabetic ulcers, becaplermin/Regranex, as a positive control which is highly efficacious in this model. Leptin receptor-deficient (db/db) male mice were sequentially assigned to treatment groups (N=10 per group) based on blood glucose levels and body weight. Mice were given a single 8 mm diameter full thickness wound on the back. Wounds were photographed and traced, and fresh test materials applied periodically with fresh dressing. Of ten mice treated with GSK2256294, three had completely healed wounds at the study conclusion, and 8/10 mice reached at least 50% closure. In the vehicle group, no mice achieved complete closure, and only 6/10 reached at least 50% closure by the study conclusion. Nine of ten wounds achieved complete closure in the positive control group by 21 days. Although the EPHX2 inhibitor results were indicative of efficacy, the single-sided p-value criterion of 0.05 was not met in this study.
The Gag Protein PEG10 Binds to RNA and Regulates Trophoblast Stem Cell Lineage Specification
Authors: Abed Mona , Verschueren Erik , Budayeva Hanna , Liu Peter , Kirkpatrick Donald S. , Reja Rohit , Kummerfeld Sarah K. , Webster Joshua D. , Gierke Sarah , Reichelt Mike , Anderson Keith R. , Newman Robert J , Roose-Girma Merone , Modrusan Zora , Pektas Hazal , Maltepe Emin , Newton Kim , Dixit Vishva M.
Published: March 2019

Peg10(paternally expressed gene 10) is an imprinted gene that is essential for placental development. It is thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag and Pol-like domains. Here we show that the Gag domain of PEG10 can promote vesicle budding similar to the HIV p24 Gag protein. Expressed in a subset of mouse endocrine organs in addition to the placenta, PEG10 was identified as a substrate of the deubiquitinating enzyme USP9X. Consistent with PEG10 having a critical role in placental development, PEG10-deficient trophoblast stem cells (TSCs) exhibited impaired differentiation into placental lineages. PEG10 expressed in wild-type, differentiating TSCs was bound to many cellular RNAs includingHbegf(Heparin-binding EGF-like growth factor), which is known to play an important role in placentation. Expression ofHbegfwas reduced in PEG10-deficient TSCs suggesting that PEG10 might bind to and stabilize RNAs that are critical for normal placental development.
Obtaining tertiary protein structures by the ab-initio interpretation of small angle X-ray scattering data
Authors: Prior Christopher , Davies Owen R , Bruce Daniel , Pohl Ehmke
Published: March 2019

Small angle X-ray scattering (SAXS) has become an important tool to investigate the structure of proteins in solution. In this paper we present a novel ab-initio method to represent polypeptide chains as discrete curves that can be used to derive a meaningful three-dimensional model from only the primary sequence and experimental SAXS data. High resolution crystal structures were used to generate probability density functions for each of the common secondary structural elements found in proteins. These are used to place realistic restraints on the model curve’s geometry. To evaluate the quality of potential models and demonstrate the efficacy of this novel technique we developed a new statistic to compare the entangled geometry of two open curves, based on mathematical techniques from knot theory. The chain model is coupled with a novel explicit hydration shell model in order derive physically meaningful 3D models by optimizing configurations against experimental SAXS data using a monte-caro based algorithm. We show that the combination of our ab-initio method with spatial restraints based on contact predictions successfully derives a biologically plausible model of the coiled–coil component of the human synaptonemal complex central element protein.

SIGNIFICANCE

Small-angle X-ray scattering allows for structure determination of biological macromolecules and their complexes in aqueous solution. Using a discrete curve representation of the polypeptide chain and combining it with empirically determined constraints and a realistic solvent model we are now able to derive realistic ab-initio 3-dimensional models from BioSAXS data. The method only require a primary sequence and the scattering data form the user.
Brand forgiveness
Authors: Fetscherin Marc , Sampedro Alexandra
Published: March 2019

Purpose

This paper aims to explore and discuss the concept of brand forgiveness. It empirically assesses the relationships among three types of brand transgressions, brand forgiveness and three consumer coping strategies.

Design/methodology/approach

A 3 × 2 research design is used to evaluate the effects of three types of brand transgression (performance, image and value) and two degrees of severity (high vs low) for brand forgiveness. Then, this paper use a 2 × 3 research design, evaluating two degrees of brand forgiveness (high vs low) together with their effects on three different consumer coping strategies (switching, attacking and purchasing again). Using a representative sample of 472 US consumers, various hypotheses related to these research designs are tested.

Findings

The results show that almost half (48 per cent) of the consumers are unlikely or very unlikely to forgive a brand compared to about a third (32 per cent) who are likely or very likely to forgive. The results of ANOVA show the more severe the brand transgression, the less likely the forgiveness. Consumers who are more likely to forgive are less likely to avoid the brand or engage in attacking behaviors; they are also more likely to purchase the brand again. The results of regression analyses show that consumers witnessing a performance-based brand transgression are more likely to forgive the brand than in the case of image- or value-based brand transgressions.

Originality/value

This paper explores and outlines the brand forgiveness construct, both theoretically and empirically.
Climate change, responsible leadership and organizational commitment
Authors: Mousa Mohamed , Puhakka Vesa , Abdelgaffar Hala A.
Published: March 2019

Purpose

The purpose of this paper is to focus on physicians in the four public hospitals located in the October province of Egypt in an attempt to explore the effect of climate change on physicians’ affective, continuance and normative commitment with and without mediating the role of responsible leadership.

Design/methodology/approach

A total of 360 physicians were contacted and all of them received a set of questionnaires. After two follow-ups, a total of 240 responses were collected with a response rate of 66.67 percent. Multiple regressions were employed to show how much variation in affective, continuance and normative commitment can be explained by climate change with and without the mediation of responsible leadership.

Findings

The findings show a statistically negative effect for climate change on physicians’ three approaches of organizational commitment (affective, continuance and normative). Furthermore, the statistical analysis proved that having responsible leaders in hospitals has a negligible effect on the relationship between climate change and the affective, continuance and normative commitment.

Originality/value

This paper contributes by filling a gap in environment and organization literature, in which empirical studies on the relationship between climate change and organizational commitment have been limited until now.
Pathways from flexible work arrangements to financial performance
Authors: Kotey Bernice Adei , Sharma Bishnu
Published: March 2019

Purpose

The purpose of this paper is to investigate the direct and indirect effects of flexible working arrangements (FWAs) on return on labour (ROL).

Design/methodology/approach

Data from 4,204 employees and their employers were used to construct regression models to assess separately, the direct relationships between the FWAs and ROL and also the indirect relationships, with job satisfaction and staff turnover as mediating variables, applying Baron and Kenny’s (1986) mediation rules.

Findings

Flexible work hours significantly and directly increased ROL and indirectly through reduction in staff turnover, while the negative direct effect of job sharing on ROL was indirectly reduced by its positive effect on job satisfaction. Time in lieu of overtime (TOIL) and working from home reduced ROL with the direct negative effects of TOIL on ROL worsened by a reduction in job satisfaction.

Practical implications

The results suggest that not all FWAs increase ROL and that the direct effects of FWAs on ROL emanate from the efficacy with which work is reallocated in FWA negotiations. The indirect effects derive from employees’ reciprocation of FWAs through improved job satisfaction and turnover. The onus is therefore, on employers to maximise returns from FWAs through efficient work reallocation during negotiations.

Originality/value

The study makes a contribution by examining the direction of effects of FWAs on ROL and the pathways (direct and indirect) by which the effects occur. Research in this area has hitherto considered subjective and qualitative performance measures. FWAs, such as job sharing and TOIL, which are rarely considered in the literature, are covered in the study.
Wildlife differentially affect tree and liana regeneration in a tropical forest: An 18‐year study of experimental terrestrial defaunation versus artificially abundant herbivores
Authors: Luskin Matthew Scott , Ickes Kalan , Yao Tze Leong , Davies Stuart J.
Published: March 2019

Hunting and land use change modify native herbivore abundances and cause cascading effects in natural ecosystems. The outcomes for vegetation depend on changes to specific plant–animal interactions, such as seed dispersal or predation, or physical disturbances.

We experimentally manipulated terrestrial wildlife populations in a primary lowland forest in Malaysia over an 18‐year period (1996–2014) to understand how artificially high or low animal densities affect tree and liana regeneration. Our study site retains a diverse wildlife community and artificially high densities of native wild pigs (Sus scrofa) that are sustained by crop raiding in distant oil palm plantations. We used fencing that excluded terrestrial animals >1 kg to experimentally simulate conditions similar to those in defaunated forests. These two treatments – abnormally high pig abundances and megafauna loss from hunting – represent common outcomes in disturbed Southeast Asian forests and are characteristic of many forests globally. We focused on trees and lianas because they are the two dominant woody life‐forms in tropical forests and crucial determinants of forest structure and function.

We found that liana sapling abundances (30–100 cm height) increased by 86% in unfenced control plots with wildlife but were stable in exclosures. In contrast, tree abundances did not change in unfenced control plots but increased by 83% in exclosures without wildlife. Evidence of scaring on surviving stems suggested that these inverted outcomes were driven by selective use of tree saplings for wild pig nests. Lianas may also have greater tolerance to wildlife disturbances like nest building. By the end of the study, lianas comprised 38% of all saplings in unfenced controls but just 14% in exclosures.

Synthesis and applications. We conclude that artificially abundant wildlife, such as crop‐raiding wild pigs, may shift tropical forest understories towards lianas while defaunation may shift it towards trees. These results highlight that ecological cascades from hunting or land use change can alter plant functional types and reshape to long‐term patterns of forest succession and change. Managing unnatural wild boar populations may be required to conserve native plant communities in both their native and exotic ranges.
How Much Do Investors Pay for Houses?
Authors: Bracke Philippe
Published: March 2019

I combine housing sales from the England and Wales Land Registry with online rental listings from property portal Zoopla to identify buy‐to‐rent transactions—known as buy‐to‐let (BTL) in the UK. These sales are procyclical, concentrated in areas where the housing market is performing well, and more common for small dwellings. Comparing these transactions against all other housing sales in 2009–2014, I show that BTL investors pay less than other buyers for the same properties. The heterogeneity of discounts across regions and property types is consistent with a simple theoretical framework that emphasizes the drivers of investors' and homeowners' demand for houses.
Prognosis for residual islet β‐cell secretion function in young patients with newly diagnosed type 1 diabetes
Authors: Miao Haitao , Zhang Juanjuan , Gu Bin , Gao Aibo , Hong Jie , Zhang Yifei , Gu Weiqiong
Published: March 2019

Background

This study investigated possible predictors of residual islet β‐cell function (RBF) in young patients with newly diagnosed type 1 diabetes (T1D).

Methods

After analyzing RBF in 443 patients with T1D according to age at diagnosis and disease duration, 110 were followed‐up over 18‐60 months. A nomogram was developed by logistic regression to explore factors associated with long‐term RBF.

Results

Of the 443 T1D patients (mean [±SD] age 20.28 ± 5.50 years; mean [±SD] diabetes duration 28.5 ± 14.6 months), RBF was preserved in 64.3%. Independent predictors for poor RBF outcome among the 110 patients in the follow‐up cohort were age at onset (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.73‐0.92; P < 0.001), high‐risk human leukocyte antigen (HLA) status (OR 4.73; CI 1.28‐17.52; P = 0.020), female sex (OR 3.39; CI 1.03‐11.22; P = 0.045), and a history of diabetic ketoacidosis (DKA; OR 8.71; CI 2.31‐32.83; P < 0.001). Baseline glutamic acid decarboxylase (GAD) antibody, family history of diabetes, body mass index, insulin dosage, and C‐peptide and HbA1c levels were not associated with poor RBF outcome. Intensive glycemic control after T1D diagnosis may improve RBF within a mean (±SD) follow‐up of 35.1 ± 13.8 months. The calibration plot for the probability of 2‐, 3‐, and 4‐year RBF showed optimal agreement between nomogram‐predicted and actual observed probabilities.

Conclusions

Younger age of onset, female sex, higher HLA risk status, and a history of DKA were the main factors predicting long‐term poor preserved β‐cell function. Glycemic control could improve RBF during the course of diabetes. The nomogram provides an individualized risk estimate of RBF in patients with newly diagnosed T1D within Chinese Han populations.
Interleukin‐6 and interleukin‐17 are related to depression in patients with rheumatoid arthritis
Authors: Li Ya‐Chi , Chou Yu‐Ching , Chen Hsiang‐Cheng , Lu Chun‐Chi , Chang Deh‐Ming
Published: March 2019

Aim

Mood disorders are a serious issue for patients with rheumatoid arthritis (RA) because poor mental health can exacerbate the disease course. This study aimed to identify the effect of proinflammatory cytokines on the mood of patients with RA.

Methods

This study was conducted at a rheumatology clinic in Northern Taiwan. In total, 113 patients with RA and 42 healthy controls were assessed for anxiety and depression symptoms using Hospital Anxiety and Depression Scale (HADS). RA was assessed using the Disease Activity Score of 28 joints (DAS28). Serum proinflammatory cytokine levels, including interleukin (IL)‐1β, IL‐6, IL‐17 and tumor necrosis factor alpha (TNF‐α) were measured and compared between different patient groups according to disease activity and pain level.

Results

Serum IL‐1β, IL‐6, IL‐17 and TNF‐α levels were significantly higher in patients with RA than in healthy controls, as were the mean anxiety and depression subscale scores. In patients with RA who had different disease activities, pain severity correlated with both anxiety and depression symptoms. When HADS scores were analyzed according to pain levels, age was correlated with depression in the severe pain group. In the mild pain group, patients with higher IL‐6 or higher IL‐17 had a higher risk of depression. There was no correlation between mood symptoms and cytokine levels in healthy controls.

Conclusion

Elevated serum IL‐6 and IL‐17 levels in patients with RA induce arthritis and cause mood symptoms, especially depression symptoms.
Dory & Nemo Early Learning Center
Authors: Chan Yee‐Ching Lilian
Published: March 2019

The case requires students to evaluate the current situation and growth options of a small business, Dory & Nemo Early Learning Center (D&N), which provides intergenerational programming to preschool children at a retirement home. The learning center was opened in September 2014, and it was able to make a small profit each year. However, it is projected that there would be a 75 percent decrease in net income from $8,072 in Fiscal 2016 to $1,819 in Fiscal 2017. Davis and Nathans, business partners of D&N, met to discuss the following growth options: (i) Mosaic Retirement Residences' proposal to set up two learning centers at their retirement homes each year for a total of six in three years and (ii) Harmony Retirement Residences' proposal for leasing space to set up learning centers at their retirement homes, one new learning center a year for a total of three in three years. Furthermore, Davis and Nathans had decided to increase the program fee from $320 to $350 per week for the 2017–18 academic session in September. They would also like to reduce their workload from 50 to 40 hours per week, increase their vacation time from two to three weeks, and increase their salaries and bonuses. Students must consider personal objectives of business partners and mission of D&N in the analysis. They learn to identify relevant information for decision making, apply appropriate analytical tools for quantitative analysis, integrate qualitative and quantitative factors in decision making, and make recommendations consistent with analysis.
Antifungals from forest trees: Usefulness in the control of etiological agents of late season soybean diseases
Authors: Sequín Christian J. , Sampietro Diego A. , Gomez Analía A. , Catalán César A.N. , Aceñolaza Pablo G.
Published: March 2019

Septoria brown spot and Cercospora leaf blight are late season diseases caused by Septoria glycines and Cercospora kikuchii, respectively. New antifungals are required against these diseases because the chemical controls currently used have detrimental impacts on wildlife and human health. In this work, 48 extracts originated from the leaves, bark, sapwood or heartwood of four forestry species were assayed by the disc diffusion method against S. glycines and C. kikuchii. Although 18 extracts showed antifungal activity, only 5 were active on both fungal species. The leaf methanolic extract of Blepharocalyx salicifolius showed the lowest minimum inhibitory dose (MID) and the highest diameter of growth inhibition (DI) on both fungal species (MID = 200 μg, DI = 14.2 mm, C. kikuchii; MID = 400 μg, DI = 12.2 mm, S. glycines). Pinocembrin was identified as the main antifungal constituent of the methanolic extract. Both the methanolic leaf extract of B. salicifolius and pinocembrin synergized in vitro the effect of the fungicide difenoconazole. Preventive applications of the extract and the mixture extract + difenoconazole (2.4 mg/mL + 0.006 mg/mL) strongly reduced disease severity generated by S. glycines and C. kikuchii 21 days after inoculation of the soybean plants. This effect was significantly stronger than that generated by difenoconazole. Our results suggest that the application of the methanolic extract of B. salicifolius, alone or in mixture with difenoconazole is a promising strategy to be incorporated in the chemical control of S. glycines and C. kikuchii.
Hormone replacement therapy attenuates hearing loss: Mechanisms involving estrogen and the IGF‐1 pathway
Authors: Williamson Tanika T. , Ding Bo , Zhu Xiaoxia , Frisina Robert D.
Published: March 2019

Estradiol (E) is a multitasking hormone that plays a prominent role in the reproductive system, and also contributes to physiological and growth mechanisms throughout the body. Frisina and colleagues have previously demonstrated the beneficial effects of this hormone, with E‐treated subjects maintaining low auditory brainstem response (ABR) thresholds relative to control subjects (Proceedings of the National Academy of Sciences of the United States of America, 2006;103:14246; Hearing Research, 2009;252:29). In the present study, we evaluated the functionality of the peripheral and central auditory systems in female CBA/CaJ middle‐aged mice during and after long‐term hormone replacement therapy (HRT) via electrophysiological and molecular techniques. Surprisingly, there are very few investigations about the side effects of HRT in the auditory system after it has been discontinued. Our results show that the long‐term effects of HRT are permanent on ABR thresholds and ABR gap‐in‐noise (GIN) amplitude levels. E‐treated animals had lower thresholds and higher amplitude values compared to other hormone treatment subject groups. Interestingly, progesterone (P)‐treated animals had ABR thresholds that increased but amplitude levels that remained relatively the same throughout treatment. These results were consistent with qPCR experiments that displayed high levels of IGF‐1R in the stria vascularis (SV) of both E and P animal groups compared to combination treatment (E + P) animals. IGF‐1R plays a vital role in mediating anti‐apoptotic responses via the PI3K/AKT pathway. Overall, our findings gain insights into the neuro‐protective properties of E hormone treatments as well as expand the scientific knowledge base to help women decide whether HRT is the right choice for them.
Naltrexone Acutely Enhances Connectivity Between the Ventromedial Prefrontal Cortex and a Left Frontoparietal Network
Authors: Elton Amanda , Dove Samantha , Spencer Cory N. , Robinson Donita L. , Boettiger Charlotte A.
Published: March 2019

Background

Naltrexone, an opioid receptor antagonist that is Food and Drug Administration approved for treating alcohol use disorder (AUD), reduces alcohol craving and intake. Despite known pharmacological properties, little is known regarding the effects of naltrexone on neural circuit function. Thus, a data‐driven examination of the neural effects of naltrexone in human subjects may offer novel insight into its treatment mechanisms.

Methods

Twenty‐one alcohol using males (22 to 39) participated in a double‐blind, placebo‐controlled crossover study of the effects of naltrexone on brain voxel‐wise functional connectivity (FC) using intersubject FC correlation mapping. We first cross‐correlated the time series from each gray matter voxel to produce a 6,356 × 6,356 FC matrix for each subject and session. We then subtracted the placebo FC matrix from the naltrexone FC matrix. To identify brain regions demonstrating significant reconfiguration of whole‐brain FC patterns following naltrexone treatment, we statistically quantified the consistency of patterns of voxel FC changes across subjects. Permutation testing identified significant clusters of voxels undergoing significant reconfiguration. Using the identified clusters in a seed‐based FC analysis, we then compared the FC patterns of affected brain areas on placebo versus naltrexone in a paired t‐test. Ridge regression analyses identified self‐report measures, including substance use, that significantly predicted individual differences in FC among naltrexone‐modulated regions.

Results

Two clusters in the rostral anterior cingulate cortex (rACC)/ventromedial prefrontal cortex (vmPFC) demonstrated significant modulation of FC by naltrexone. Using these 2 proximal clusters as a single seed, specific FC changes were identified in regions associated with a left frontoparietal network (increasing), as well as visual and motor regions (decreasing). Stronger FC between the rACC/vmPFC and this set of regions on placebo was associated with more external locus of control, whereas weaker connectivity was associated with greater substance use problems. Naltrexone strengthened these connections most among individuals who reported greater drinking to cope.

Conclusions

Enhancing connectivity between the rACC/vmPFC, implicated in alcohol craving, and components of a left frontoparietal network involved in executive control may represent an effective strategy for the treatment of AUD.
‘Bee aware’ when weeding! Network analysis of bee‐flower visits in the Victorian Alps
Authors: Ng Kat
Published: March 2019

This commentary is for the following article:
Androgen receptor antagonism accelerates disease onset in the SOD1G93A mouse model of amyotrophic lateral sclerosis
Authors: McLeod Victoria M. , Lau Chew L. , Chiam Mathew D.F. , Rupasinghe Thusitha W. , Roessner Ute , Djouma Elvan , Boon Wah C. , Turner Bradley J.
Published: March 2019

Background and Purpose

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease typically more common in males, implicating androgens in progression of both patients and mouse models. Androgen effects are mediated by androgen receptor which is highly expressed in spinal motor neurons and skeletal muscles. To clarify the role of androgen receptors in ALS, we therefore examined the effect of androgen receptor antagonism in the SOD1G93A mouse model.

Experimental Approach

The androgen receptor antagonist, flutamide, was administered to presymptomatic SOD1G93A mice as a slow‐release subcutaneous implant (5 mg·day−1). Testosterone, flutamide, and metabolite levels were measured in blood and spinal cord tissue by LC–MS–MS. Effects on disease onset and progression were assessed using motor function tests, survival, muscle, and neuropathological analyses.

Key Results

Flutamide was metabolised to 2‐hydroxyflutamide achieving steady‐state plasma levels across the study duration and reached the spinal cord at pharmacologically active concentrations. Flutamide treatment accelerated disease onset and locomotor dysfunction in male SOD1G93A mice, but not female mice, without affecting survival. Analysis of hindlimb muscles revealed exacerbation of myofibre atrophy in male SOD1G93A mice treated with flutamide, although motor neuron pathology was not affected.

Conclusion and Implications

The androgen receptor antagonist accelerated disease onset in male SOD1G93A mice, leading to exacerbated muscle pathology, consistent with a role of androgens in modulating disease severity, sexual dimorphism, and peripheral pathology in ALS. These results also demonstrate a key contribution of skeletal muscle pathology to disease onset, but not outcome, in this mouse model of ALS.
It looks like childhood eczema but is it?
Authors: Mortz Charlotte G. , Brockow Knut , Bindslev‐Jensen Carsten , Broesby‐Olsen Sigurd
Published: March 2019

In childhood, the most common type of eczema/dermatitis is atopic dermatitis, which occurs in up to 25% of children world‐wide. However, the diagnosis may sometimes be challenging and atopic dermatitis may resemble other types of dermatitis as well as other skin diseases such as psoriasis, infections, infestations and malignancies as well as metabolic, genetic and autoimmune disorders. This review will focus on how to recognize the most common types of dermatitis in children and adolescents and how to separate them from the most common differential diagnoses clinically and histologically.
Lic regulates JNK‐mediated cell death in Drosophila
Authors: Sun Yihao , Zhang Di , Li Chenglin , Huang Jiuhong , Li Wenzhe , Qiu Yu , Mao Aiwu , Zhou Mingcheng , Xue Lei
Published: March 2019

Objectives

The evolutionary conserved JNK pathway plays crucial role in cell death, yet factors that modulate this signalling have not been fully disclosed. In this study, we aim to identify additional factors that regulate JNK signalling in cell death, and characterize the underlying mechanisms.

Materials and Methods

Drosophila were raised on standard media, and cross was carried out at 25°C. The Gal4/UAS system was used to express proteins or RNAi in a specific temporal and spatial pattern. Gene expression was revealed by GFP fluorescence, X‐gal staining or immunostaining of 3rd instar larval eye and wing discs. Cell death was visualized by acridine orange (AO) staining. Images of fly eyes and wings were taken by OLYMPUS microscopes.

Results

We found that licorne (lic) encoding the Drosophila MKK3 is an essential regulator of JNK‐mediated cell death. Firstly, loss of lic suppressed ectopic Egr‐triggered JNK activation and cell death in eye and wing development. Secondary, lic is necessary for loss‐of‐cell polarity‐induced, physiological JNK‐dependent cell death in wing development. Thirdly, Lic overexpression is sufficient to initiate JNK‐mediated cell death in developing eyes and wings. Furthermore, ectopic Lic activates JNK signalling by promoting JNK phosphorylation. Finally, genetic epistatic analysis confirmed that Lic acts in parallel with Hep in the Egr‐JNK pathway.

Conclusions

This study not only identified Lic as a novel component of the JNK signalling, but also disclosed the crucial roles and mechanism of Lic in cell death.
Gene signatures common to allograft rejection are associated with lymphocytic bronchitis
Authors: Greenland John R. , Wang Ping , Brotman Joshua J. , Ahuja Rahul , Chong Tiffany A. , Kleinhenz Mary Ellen , Leard Lorriana E. , Golden Jeffrey A. , Hays Steven R. , Kukreja Jasleen , Singer Jonathan P. , Rajalingam Raja , Jones Kirk , Laszik Zoltan G. , Trivedi Neil N. , Greenland Nancy Y. , Blanc Paul D.
Published: March 2019

Lymphocytic bronchitis (LB) precedes chronic lung allograft dysfunction. The relationships of LB (classified here as Endobronchial or E‐grade rejection) to small airway (A‐ and B‐grade) pathologies are unclear. We hypothesized that gene signatures common to allograft rejection would be present in LB. We studied LB in two partially overlapping lung transplant recipient cohorts: Cohort 1 included large airway brushes (6 LB cases and 18 post‐transplant referents). Differential expression using DESeq2 was used for pathway analysis and to define an LB‐associated metagene. In Cohort 2, eight biopsies for each pathology subtype were matched with pathology‐free biopsies from the same subject (totaling 48 samples from 24 subjects). These biopsies were analyzed by multiplexed digital counting of immune transcripts. Metagene score differences were compared by paired t tests. Compared to referents in Cohort 1, LB demonstrated upregulation of allograft rejection pathways, and upregulated genes in these cases characterized an LB‐associated metagene. We observed statistically increased expression in Cohort 2 for this LB‐associated metagene and four other established allograft rejection metagenes in rejection vs paired non‐rejection biopsies for both E‐grade and A‐grade subtypes, but not B‐grade pathology. Gene expression‐based categorization of allograft rejection may prove useful in monitoring lung allograft health.
A Brave New World, or the Same Old Story with New Characters?
Authors: Ghosh Jayati
Published: March 2019

Capitalism has always been a global system, but not in fixed ways. Different national powers have emerged and become dominant over the centuries, but the fundamental processes underlying the uneven development of global capitalism have not altered; they continue to be driven by imperialism — the struggle of large capital over economic territory of various kinds. Since the late 1960s, only the East Asian region has shown notable increases in its share of global GDP, and for the last two decades this has been dominated by the rise of China. This is directly related to the ability of the Chinese state to control the economy and to implement heterodox policies with very high investment rates. However, the Chinese case is exceptional: few other developing countries have followed a trajectory anything like that of China. Meanwhile, internal inequalities have increased across the world, as the bargaining power of capital vis‐à‐vis labour has increased dramatically in every country. This reflects the changed form of 21stcentury imperialism, which relies increasingly on the international legal and regulatory architecture as fortified by various multilateral, plurilateral and bilateral agreements that establish the hegemony of global capital in different ways.
Gender Blindness and the Annulment of the Development Contract
Authors: Alemany Cecilia , Slatter Claire , Rodríguez Enríquez Corina
Published: March 2019

This contribution to the Forum Debate responds to Horner and Hulme's analysis on the ‘rise of the South’, which they see as suggesting a dramatic redrawing of the global map of development and inequality. This response presents a critical South feminist perspective, informed by the lived realities of women in the South. It is based on a historical and political perspective that goes beyond income inequality to understand gender inequality in development within the persistent North–South divide.
Equality‐led Development and the Demand‐ and Supply‐side Effects
Authors: Onaran Özlem
Published: March 2019

This contribution to the Forum Debate on global development focuses on the dimension of functional income distribution between labour and capital and its demand‐side and supply‐side effects. The article summarizes recent literature that has sought to explain the reasons behind the global fall in the labour share. It then discusses the demand‐side effects of the declining wage share on growth, based on the post‐Keynesian/post‐Kaleckian literature. The author presents an alternative policy scenario for the G20 based on a mix of increasing wage share and public investment, before discussing the supply‐side effects of rising inequality. The article concludes with some policy implications for equality‐led development.
When do herbivorous insects compete? A phylogenetic meta‐analysis
Authors: Bird Gwendolyn , Kaczvinsky Chloe , Wilson Alan E. , Hardy Nate B.
Published: March 2019

When herbivorous insects interact, they can increase or decrease each other's fitness. As it stands, we know little of what causes this variation. Classic competition theory predicts that competition will increase with niche overlap and population density. And classic hypotheses of herbivorous insect diversification predict that diet specialists will be superior competitors to generalists. Here, we test these predictions using phylogenetic meta‐analysis. We estimate the effects of diet breadth, population density and proxies of niche overlap: phylogenetic relatedness, physical proximity and feeding‐guild membership. As predicted, we find that competition between herbivorous insects increases with population density as well as phylogenetic and physical proximity. Contrary to predictions, competition tends to be stronger between than within feeding guilds and affects specialists as much as generalists. This is the first statistical evidence that niche overlap increases competition between herbivorous insects. However, niche overlap is not everything; complex feeding guild effects indicate important indirect interactions.
Limits‐to‐arbitrage, investment frictions, and the investment effect: New evidence
Authors: Lam F. Y. Eric C. , Li Ya , Prombutr Wikrom , Wei K. C. John
Published: March 2019

This study comprehensively reexamines the debate over behavioral and rational explanations for the investment effect in an updated sample. We closely follow the previous literature and provide several differences. Our tests include five prominent measures of corporate investment and corporate profitability in q‐theory and recent investment‐based asset pricing models. Both classical and Bayesian inferences show that limits‐to‐arbitrage tend to be supported by more evidence than investment frictions for all investment measures. When idiosyncratic volatility and cash flow volatility are used in measuring investment frictions, the inference is more favorable for the rational explanation.
Application and indications of magnetic resonance imaging and computed tomography of the equine head
Authors: Manso‐Díaz G. , Taeymans O. , García‐López J. M. , Weller R.
Published: March 2019

The equine head is an anatomically highly complex area affected by a range of disorders, making the diagnosis of head conditions challenging. Imaging techniques play a crucial role in the diagnostic work‐up of head disorders. Tomographic imaging methods, such as computed tomography (CT) and magnetic resonance imaging (MRI) are particularly useful in avoiding problems associated with superimposition of multiple structures in this highly complex region. Both techniques are becoming more widely available in equine medicine. However, the choice between CT and MRI for imaging the equine head is not always straightforward. Each modality has advantages and disadvantages in terms of practicality, costs and diagnostic value for particular problems. The aim of this review is to describe the application of CT and MRI for imaging the equine head and to provide a practical guide for their use in different anatomical structures and clinical indications. This should allow the equine practitioner to make an informed decision on which modality to choose.
Accounting for spectroscopic effects in laser‐based open‐path eddy covariance flux measurements
Authors: Burba George , Anderson Tyler , Komissarov Anatoly
Published: March 2019

A significant portion of the production and consumption of trace gases (e.g. CO2, CH4, N2O, NH3, etc.) by world ecosystems occurs in areas without sufficient infrastructure or easily available grid power to run traditional closed‐path flux stations. Open‐path analyzer design allows such measurements with power consumption 10–150 times below present closed‐path technologies, helping to considerably expand the global coverage and improve the estimates of gas emissions and budgets, informing the remote sensing and modeling communities and policy decisions, all the way to IPCC reports. Broad‐band nondispersive infrared devices have been used for open‐path CO2 and H2O measurements since the late 1970s, but since recently, a growing number of new narrow‐band laser‐based instruments are being rapidly developed. The new design comes with its own challenges, specifically: (a) mirror contamination, and (b) uncontrolled air temperature, pressure and humidity, affecting both the gas density and the laser spectroscopy of the measurements. While the contamination can be addressed via automated cleaning, and density effects can be addressed via the Webb‐Pearman‐Leuning approach, the spectroscopic effects of the in situ temperature, pressure and humidity fluctuations on laser‐measured densities remain a standing methodological question. Here we propose a concept accounting for such effects in the same manner as Webb et al. proposed to account for respective density effects. Derivations are provided for a general case of flux of any gas, examined using a specific example of CH4 fluxes from a commercially available analyzer, and then tested using “zero‐flux” experiment. The proposed approach helps reduce errors in open‐path, enclosed, and temperature‐ or pressure‐uncontrolled closed‐path laser‐based flux measurements due to the spectroscopic effects from few percents to multiple folds, leading to methodological advancement and geographical expansion of the use of such systems providing reliable and consistent results for process‐level studies, remote sensing and Earth modeling applications, and GHG policy decision‐making.
Chemical, cytotoxic and genotoxic analysis of etidronate in sodium hypochlorite solution
Authors: Ballal N. V. , Das S. , Rao B. S. S. , Zehnder M. , Mohn D.
Published: March 2019

Aim

To test whether the incorporation of a chelation powder, etidronate, marketed for root canal irrigation (Dual Rinse HEDP) into a sodium hypochlorite (NaOCl) solution induced additional cytotoxic and genotoxic effects not observed with NaOCl alone.

Methodology

Fresh and 24‐h‐old mixtures of 0.9 g of etidronate in 10 mL of 2.5% NaOCl were assessed for their basic chemical features including pH and the ability to chelate Ca2+ from hydroxylapatite. Pure NaOCl and phosphate‐buffered saline (PBS) with/without etidronate served as control solutions. Cytotoxic and genotoxic effects of diluted solutions (1:10, 1:100, and 1:1000) were assessed on Chinese hamster lung fibroblast (V79) using the MTT, clonogenic and micronucleus assays, respectively. One‐way ANOVA and Tukey's HSD test were applied with an alpha‐type error of 5% (P < 0.05).

Results

In mixtures of NaOCl and etidronate, the free available chlorine was lost completely after 24 h, and the pH dropped by more than 3 units. However, the ability of the etidronate to chelate Ca2+ was maintained. The fresh mixtures of NaOCl and etidronate were not more toxic than NaOCl alone (P > 0.05), whilst the 24‐h‐old mixtures were less toxic (P < 0.05) and statistically similar to pure etidronate. Etidronate per se showed little cytotoxicity and no genotoxicity at the tested dilutions.

Conclusions

The ability of the used etidronate, Dual Rinse HEDP, to chelate calcium is not affected by NaOCl. Cytotoxicity and genotoxicity of mixed solutions is dictated by the presence of free available chlorine therein.