bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the Cause of Anuria Post Kidney Transplantation by Renal Scintigraphy
Authors: Van Keerberghen Ciska-Anne , Naesens Maarten , Gheysens Olivier , Jochmans Ina , Pirenne Jacques , Goffin Karolien
Published: September 2018

A dynamic renal scintigraphy is widely used after renal transplantation to evaluate transplant function and possible complications. We report the case of a 27-year-old man with persisting anuria after kidney transplantation. A renal scintigraphy using 99mTc-ethylenedicysteine followed by SPECT/CT of the abdomen was performed showing tracer accumulation in the colon without any activity in the bladder, as a result of ureter reimplantation onto the sigmoid instead of onto the previously reconstructed bladder. Renal scintigraphy identified the cause and localization of the urinary leak, which led to immediate surgical reimplantation of the ureter onto the augmented bladder with onset of diuresis.
Pretreatment Primary Tumor and Nodal SUVmax Values on 18F-FDG PET/CT Images Predict Prognosis in Patients With Salivary Gland Carcinoma
Authors: Hsieh Cheng-En , Cheng Nai-Ming , Chou Wen-Chi , Venkatesulu Bhanu Prasad , Chou Yung-Chih , Liao Chun-Ta , Yen Tzu-Chen , Lin Chien-Yu
Published: September 2018

Purpose

To assess whether primary tumor and nodal 18F-FDG uptake may predict prognosis in patients with salivary gland carcinoma.

Methods

We conducted a 2-center, retrospective study on 117 patients with salivary gland carcinoma who underwent 18F-FDG PET/CT before treatment and were subsequently treated with curative intent between 2004 and 2014. Pretreatment SUVmax of the primary tumor (SUVmax-T) and that of positive nodes (SUVmax-N) were analyzed in relation to clinical outcomes.

Results

Patients were followed up for a median of 61 months. The following 5-year rates were observed: locoregional control (LRC), 78%; distant metastasis-free survival (DMFS), 67%; progression-free survival (PFS), 62%; and overall survival (OS), 68%. A cutoff value of 7.0 maximized the prognostic impact of both SUVmax-T and SUVmax-N for PFS. Compared with patients with SUVmax-T and SUVmax-N values below the optimal cutoff, those with SUVmax-T and SUVmax-N of 7 or greater showed less favorable 5-year LRC (P < 0.001 and P < 0.001), DMFS (P < 0.001 and P < 0.001), PFS (P < 0.001 and P < 0.001), and OS (P < 0.001 and P < 0.001) rates. Both SUVmax-T of 7 or greater and SUVmax-N of 7 or greater were identified as independent predictors of LRC (P = 0.010 and 0.022), DMFS (P = 0.001 and P = 0.001), PFS (P < 0.001 and P = 0.007), and OS (P = 0.007 and P = 0.002) in multivariable analysis. We therefore devised a prognostic scoring system based on these 2 variables, which was found to be strongly associated with 5-year LRC (P < 0.001), DMFS (P < 0.001), PFS (P < 0.001), and OS (P < 0.001) rates.

Conclusions

SUVmax of the primary tumor and SUVmax-N on pretreatment 18F-FDG PET/CT images may be a useful guide in predicting treatment outcomes, especially when combined in a prognostic scoring system.
Incidental Detection of Skeletal Metastases on 99mTc-DTPA Renography
Authors: Seniaray Nikhil , Verma Ritu , Belho Ethel S. , Mahajan Harsh
Published: September 2018

We present the case of a 53-year-old man with left hydroureteronephrosis who underwent 99mTc-DTPA renography for functional assessment of bilateral kidneys. 99mTc-DTPA renography of the patient showed diffusely increased extrarenal 99mTc-DTPA uptake in the visualized lumbosacral vertebrae and in the pelvic bones, on the blood flow and functional phase of the renography, which was suggestive of disseminated skeletal disease. Subsequent MRI lumbosacral spine and 18F-FDG PET/CT revealed extensive skeletal metastases corresponding to the increased extrarenal 99mTc-DTPA uptake in the lumbosacral vertebrae and the pelvic bones from primary left lung mitotic lesion.
Benign Esophageal Findings on 68Ga–Prostate-Specific Membrane Antigen PET/CT Scan
Authors: Jochumsen Mads Ryø , Klingenberg Søren , Bouchelouche Kirsten
Published: September 2018

In 2 high-risk prostate cancer patients, PET scans revealed focally increased 68Ga–prostate-specific membrane antigen uptake in the distal esophagus. Both patients had hiatus herniation on gastroscopy, and esophageal biopsies revealed acute and chronic inflammation in both patients and a benign hyperplastic polyp in one of the patients. Recently, reports have demonstrated that inflammation can cause false-positive findings on 68Ga–prostate-specific membrane antigen PET/CT, and these cases present this phenomenon in the esophagus as well.
Early Hypertension and Diabetes After Living Kidney Donation: A National Cohort Study
Authors: Holscher Courtenay M. , Bae Sunjae , Thomas Alvin G. , Henderson Macey L. , Haugen Christine E. , DiBrito Sandra R. , Muzaale Abimereki D. , Garonzik Wang Jacqueline M. , Massie Allan B. , Lentine Krista L. , Segev Dorry L.
Published: September 2018

Background.

Living kidney donors have an increased risk of end-stage renal disease, with hypertension and diabetes as the predominant causes. In this study, we sought to better understand the timeline when these diseases occur, focusing on the early postdonation period.

Methods.

We studied 41 260 living kidney donors in the United States between 2008 and 2014 from the Scientific Registry of Transplant Recipients and modeled incidence rates and risk factors for hypertension and diabetes.

Results.

At 6 months, 1 year, and 2 years postdonation, there were 74, 162, and 310 cases, respectively, of hypertension per 10 000 donors. Donors who were older (per 10 y, adjusted incidence rate ratio [aIRR], 1.40; 95% confidence interval [CI], 1.29-1.51), male (aIRR, 1.31; 95% CI, 1.14-1.50), had higher body mass index (per 5 units, aIRR, 1.29; 95% CI, 1.17-1.43), and were related to their recipient (first-degree relative: aIRR, 1.28; 95% CI, 1.08-1.52; spouse: aIRR, 1.34; 95% CI, 1.08-1.66) were more likely to develop hypertension, whereas donors who were Hispanic/Latino were less likely (aIRR, 0.71; 95% CI, 0.55-0.93). At 6 months, 1 year, and 2 years, there were 2, 6, and 15 cases of diabetes per 10 000 donors. Donors who were older (per 10 y: aIRR, 1.42; 95% CI, 1.11-1.82), had higher body mass index (per 5 units: aIRR, 1.52; 95% CI, 1.04-2.21), and were Hispanic/Latino (aIRR, 2.45; 95% CI, 1.14-5.26) were more likely to develop diabetes.

Conclusions.

In this national study, new-onset diabetes was rare, but 3% of donors developed hypertension within 2 years of nephrectomy. These findings reaffirm that disease pathways for kidney failure differ by donor phenotype and estimate the population most at-risk for later kidney failure.
Building Kidney Exchange Programmes in Europe—An Overview of Exchange Practice and Activities
Authors: Biró Péter , Haase-Kromwijk Bernadette , Andersson Tommy , Ásgeirsson Eyjólfur Ingi , Baltesová Tatiana , Boletis Ioannis , Bolotinha Catarina , Bond Gregor , Böhmig Georg , Burnapp Lisa , Cechlárová Katarína , Di Ciaccio Paola , Fronek Jiri , Hadaya Karine , Hemke Aline , Jacquelinet Christian , Johnson Rachel , Kieszek Rafal , Kuypers Dirk R. , Leishman Ruthanne , Macher Marie-Alice , Manlove David , Menoudakou Georgia , Salonen Mikko , Smeulders Bart , Sparacino Vito , Spieksma Frits C.R. , Valentín María Oliva , Wilson Nic , van der Klundert Joris
Published: September 2018

Background.

Considerable differences exist among the living donor Kidney Exchange Programmes (KEPs) that are in use and being built in Europe, contributing to a variation in the number of living donor transplants (Newsletter Transplant; International figures on donation and transplantation 2016). Efforts of European KEPs to exchange (best) practices and share approaches to address challenges have, however, been limited.

Methods.

Experts from 23 European countries, collaborating on the European Network for Collaboration on Kidney Exchange Programmes Cooperation on Science and Technology Action, developed a questionnaire to collect detailed information on the functioning of all existing KEPs in Europe, as well as their opportunities and challenges. Following a comparative analysis, results were synthesized and interpreted by the same experts.

Results.

The practices, opportunities and challenges reported by 17 European countries reveal that some of the 10 operating programs are mature, whereas others are in earlier stages of development. Over 1300 transplants were performed through existing KEPs up to the end of 2016, providing approximately 8% of their countries’ living kidney donations in 2015. All countries report challenges to either initiating KEPs or increasing volumes. Some challenges are shared, whereas others differ because of differences in context (eg, country size, effectiveness of deceased donor program) and ethical and legal considerations (eg, regarding living donation as such, nonrelated donors, and altruistic donation). Transnational initiatives have started in Central Europe, Scandinavia, and Southern Europe.

Conclusions.

Exchange of best practices and shared advancement of national programs to address existing challenges, aided by transnational exchanges, may substantially improve access to the most (cost) effective treatment for the increasing number of patients suffering from kidney disease.
The Use of Donation After Circulatory Death Organs for Simultaneous Liver-kidney Transplant: To DCD or Not to DCD?
Authors: Vinson Amanda Jean , Gala-Lopez Boris , Tennankore Karthik , Kiberd Bryce
Published: September 2018

Background.

Because of the challenges with organ scarcity, many centers performing simultaneous liver-kidney transplant (SLKT) are opting to accept donation after circulatory death (DCD) organs as a means of facilitating earlier transplant and reducing death rates on the waitlist. It has been suggested, however, that DCD organs may have inferior graft and patient survival posttransplant compared with donation after neurologic death (DND) organs.

Methods.

We created a Markov model to compare the overall outcomes of accepting a DCD SLKT now versus waiting for a DND SLKT in patients waitlisted for SLKT, stratified by base Model for End-Stage Liver Disease (MELD) score (≤20, 21–30, >30).

Results.

Waiting for DND SLKT was the preferred treatment strategy for patients with a MELD score of 30 or less (incremental value of 0.54 and 0.36 quality-adjusted life years for MELD score of 20 or less and MELD score of 21 to 30 with DND versus DCD SLKT, respectively). The option to accept a DCD SLKT became the preferred choice for those with a MELD score greater than 30 (incremental value of 0.31 quality-adjusted life years for DCD versus DND SLKT). This finding was confirmed in a probabilistic sensitivity analysis and persisted when analyzing total life years obtained for accept DCD versus do not accept DCD.

Conclusions.

There is a benefit to accepting DCD SLKT for patients with MELD score greater than 30. Although not accepting DCD SLKT and waiting for DND SLKT is the preferred option for patients with MELD of 30 or less, the incremental value is small.
NKG2C Natural Killer Cells in Bronchoalveolar Lavage Are Associated With Cytomegalovirus Viremia and Poor Outcomes in Lung Allograft Recipients
Authors: Calabrese Daniel R. , Chong Tiffany , Wang Angelia , Singer Jonathan P. , Gottschall Marc , Hays Steven R. , Golden Jeffrey A. , Kukreja Jasleen , Lanier Lewis L. , Tang Qizhi , Greenland John R.
Published: September 2018

Background.

Cytomegalovirus (CMV) infection is a risk factor for chronic lung allograft dysfunction (CLAD), which limits survival in lung allograft recipients. Natural killer (NK) cells that express the NKG2C receptor mediate CMV-specific immune responses. We hypothesized that NKG2C+ NK cells responding to CMV in the lung allograft would reduce CMV-related inflammation and would improve CLAD-free survival.

Methods.

We prospectively followed 130 subjects who underwent lung transplantation from 2012 to 2016. Bronchoalveolar lavage (BAL) NK cells were immunophenotyped for NKG2C, maturation, and proliferation markers. CMV viral load, serologies, serial spirometry, and mortality were recorded from medical records. Natural killer cell subset association with CMV endpoints were made using generalized estimating equation-adjusted linear models. BAL NKG2C+ NK cell association with CLAD-free survival was assessed by Cox proportional hazards modeling.

Results.

NKG2C+ NK cells were more mature and proliferative than NKG2C− NK cells and represented a median of 7.8% of BAL NK cells. The NKG2C+ NK cell proportion increased prior to the first detection of viremia and was nearly tripled in subjects with high level viremia (>1000 copies/mL) compared with no detected viremia. Subjects with increased BAL NKG2C+ NK cells, relative to the median, had a significantly increased risk for CLAD or death (hazard ratio, 4.2; 95% confidence interval, 1.2–13.3).

Conclusions.

The BAL NKG2C+ NK cell proportion may be a relevant biomarker for assessing risk of CMV viremia and quantifying potential CMV-related graft injury that can lead to CLAD or death.
IL-17A Is Critical for CD8+ T Effector Response in Airway Epithelial Injury After Transplantation
Authors: Zhang Ruochan , Fang Huihui , Chen Rongjuan , Ochando Jordi C. , Ding Yaozhong , Xu Jiangnan
Published: September 2018

Background

Airway epithelium is the primary target of trachea and lung transplant rejection, the degree of epithelial injury is closely correlated with obliterative bronchiolitis development. In this study, we investigated the cellular and molecular mechanisms of IL-17A-mediated airway epithelial injury after transplantation.

Methods

Murine orthotopic allogeneic trachea or lung transplants were implemented in wild type or RORγt−/− mice. Recipients received anti-IL-17A or anti-IFNγ for cytokine neutralization, anti-CD8 for CD8+ T-cell depletion, or STAT3 inhibitor to suppress type 17 CD4+/CD8+ T cell development. Airway injury and graft inflammatory cell infiltration were examined by histopathology and immunohistochemistry. Gene expression of IL-17A, IFNγ, perforin, granzyme B, and chemokines in grafts was quantitated by real-time RT-PCR.

Results

IL-17A and IFNγ were rapidly expressed and associated with epithelial injury and CD8+ T-cell accumulation after allotransplantation. Depletion of CD8+ T cells prevented airway epithelial injury. Neutralization of IL-17A or devoid of IL-17A production by RORγt deficiency improved airway epithelial integrity of the trachea allografts. Anti–IL-17A reduced the expression of CXCL9, CXCL10, CXCL11, and CCL20, and abolished CD8+ T-cell accumulation in the trachea allografts. Inhibition of STAT3 activation significantly reduced IL-17A expression in both trachea and lung allografts; however, it increased IFNγ expression and cytotoxic activities, which resulted in the failure of airway protection.

Conclusions

Our data reveal the critical role of IL-17A in mediating CD8+ T effector response that causes airway epithelial injury and lung allograft rejection, and indicate that inhibition of STAT3 signals could drive CD8+ T cells from Tc17 toward Tc1 development.
The evolution of plate tectonics
Authors: Stern Robert J.
Published: October 2018

To understand how plate tectonics became Earth's dominant mode of convection, we need to address three related problems. (i) What was Earth's tectonic regime before the present episode of plate tectonics began? (ii) Given the preceding tectonic regime, how did plate tectonics become established? (iii) When did the present episode of plate tectonics begin? The tripartite nature of the problem complicates solving it, but, when we have all three answers, the requisite consilience will provide greater confidence than if we only focus on the long-standing question of when did plate tectonics begin? Earth probably experienced episodes of magma ocean, heat-pipe, and increasingly sluggish single lid magmatotectonism. In this effort we should consider all possible scenarios and lines of evidence. As we address these questions, we should acknowledge there were probably multiple episodes of plate tectonic and non-plate tectonic convective styles on Earth. Non-plate tectonic styles were probably dominated by ‘single lid tectonics’ and this evolved as Earth cooled and its lithosphere thickened. Evidence from the rock record indicates that the modern episode of plate tectonics began in Neoproterozoic time. A Neoproterozoic transition from single lid to plate tectonics also explains kimberlite ages, the Neoproterozoic climate crisis and the Neoproterozoic acceleration of evolution.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics’.
The dependence of planetary tectonics on mantle thermal state: applications to early Earth evolution
Authors: Foley Bradford J.
Published: October 2018

For plate tectonics to operate on a planet, mantle convective forces must be capable of forming weak, localized shear zones in the lithosphere that act as plate boundaries. Otherwise, a planet's mantle will convect in a stagnant lid regime, where subduction and plate motions are absent. Thus, when and how plate tectonics initiated on the Earth is intrinsically tied to the ability of mantle convection to form plate boundaries; however, the physics behind this process are still uncertain. Most mantle convection models have employed a simple pseudoplastic model of the lithosphere, where the lithosphere ‘fails’ and develops a mobile lid when stresses in the lithosphere reach the prescribed yield stress. With pseudoplasticity high mantle temperatures and high rates of internal heating, conditions relevant for the early Earth, impede plate boundary formation by decreasing lithospheric stresses, and hence favour a stagnant lid for the early Earth. However, when a model for shear zone formation based on grain size reduction is used, early Earth thermal conditions do not favour a stagnant lid. While lithosphere stress drops with increasing mantle temperature or heat production rate, the deformational work, which drives grain size reduction, increases. Thus, the ability of convection to form weak plate boundaries is not impeded by early Earth thermal conditions. However, mantle thermal state does change the style of subduction and lithosphere mobility; high mantle temperatures lead to a more sluggish, drip-like style of subduction. This ‘sluggish lid’ convection may be able to explain many of the key observations of early Earth crust formation processes preserved in the geologic record. Moreover, this work highlights the importance of understanding the microphysics of plate boundary formation for assessing early Earth tectonics, as different plate boundary formation mechanisms are influenced by mantle thermal state in fundamentally different ways.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics’.
Laboratory investigation of mechanisms for phase mixing in olivine + ferropericlase aggregates
Authors: Wiesman Harison S. , Zimmerman Mark E. , Kohlstedt David L.
Published: October 2018

To investigate the role of grain boundary pinning and the mechanisms by which phase mixing occurs during deformation of polymineralic rocks, we conducted high-strain torsion experiments on samples consisting of olivine plus 30 vol% ferropericlase. Experiments were performed in a gas-medium deformation apparatus at 1524 K and 300 MPa. Samples were deformed to outer radius shear strains of up toγ(R) = 14.1. The value of the stress exponent and the small grain sizes of our samples indicate that our two-phase material deformed by dislocation-accommodated grain boundary sliding. In samples deformed to 1 < γ < 7, elongated clusters of ferropericlase grains form thin layers in the olivine matrix, and small grains of ferropericlase appear at olivine grain boundaries and three- and four-grain junctions. Byγ ≈ 14, a well-distributed mixture of small ferropericlase grains among the olivine grains developed. Microstructures exhibit similarities to both mechanical and chemical models proposed to describe the processes leading to phase mixing. Our results provide evidence for grain size reduction during phase mixing that results in a grain size significantly smaller than the value predicted by the single-phase recrystallization piezometer for olivine. Thus, phase mixing provides a mechanism for the persistent weakening of rocks that is important for developing and maintaining shear zones necessary for plate tectonics.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics'.
Early earth geodynamics: cross examining the geological testimony
Authors: Kemp Anthony I. S.
Published: October 2018

Many studies link the presence of continents on Earth to the operation of plate tectonics. Radiogenic isotope data have, however, long consigned the bulk of crust generation and preservation to the murky realm of the Precambrian Earth, where the prevailing geodynamic systems are highly uncertain due to the sparse and complex nature of the geological record of these early eons. The purpose of this paper is to examine the nature of this geological record, considering the biases and artefacts that may undermine its fidelity, and to assess what are the most robust lines of evidence from which meaningful geodynamic inferences can be drawn. This is pursued with reference to Hadean detrital zircons, Archean gneiss complexes and Archean granite–greenstone terranes, and by considering isotopic proxies of crust–mantle interaction. The evidence reinforces long held views that the formation of some of the oldest continental nuclei involved a distinctive mode of planetary geodynamics that rests uneasily within definitions of modern style plate tectonics. A detailed interrogation of the oldest rocks, integrating multi-scale information from the best preserved whole-rock and mineral archives, and emphasizing careful selection at the sampling and analytical stages, will lead to the most robust input data for petrological and thermodynamic models of early Earth processes.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics’.
Adaption of artificial microvascular networks
Authors: Fredrich Thierry , Welter Michael , Rieger Heiko
Published: September 2018

We explored the application of the adaption algorithm introduced by Secomb et. al. to artificial blood vessel networks and find that the resulting networks to not obey Murray’s law. The reported analysis and visual examples document the contrast between two different types of networks. We conjecture that an interrupt of an established signaling cascade could be a hallmark of solid vascular tumors.
Feeding location of aphid prey affects life history traits of a native predator
Authors: Cibils-Stewart Ximena , Nechols James , Giles Kristopher , McCornack Brian P.
Published: October 2018

The green peach aphid (GPA),Myzus persicae S., and the cabbage aphid (CA),Brevicoryne brassicae L., exhibit a feeding preference when exposed to different canola (Brassica napus L.) plant structures. Preference may be associated with the concentration and/or composition of allelochemicals; specifically, glucosinolates (GLS). Furthermore, each aphid species employs a different strategy for tolerating plant defensive chemistry; GPA excretes glucosinolates while CA sequesters these toxic compounds. Given these different detoxification mechanisms, it is possible that both feeding location and aphid species may affect prey suitability forHippodamia convergenslarvae. We conducted a factorial laboratory experiment to evaluate whether one or both factors impacted predator fitness. We hypothesized that plant structures with higher GLS concentrations will negatively affect the development and survival of immature predators, which will also vary based on prey detoxification strategies. Results confirm that when predators fed on either aphid species reared on canola structures having lower GLS concentrations, development was faster than when they fed on aphids reared on structures having higher GLS. Although predators consumed more GPA than CA, consumption rates did not differ between rearing location for GPA, but fewer CA were consumed when reared on reproductive canola parts. These findings suggest that: 1) plant-mediated differences in prey quality exist for canola aphids; 2) the type of adaptation used by aphids to overcome plant defenses have important consequences for prey suitability; and 3) reduced feeding byH. convergenslarvae on unsuitable prey may offset deleterious effects of plant defenses against aphid pests. By evaluating source-sink dynamics at the plant level, we can further understand trophic interactions involving plant defenses and how these interactions may influence community dynamics and structure.
Evaluating intraspecific genetic diversity of a fish population using environmental DNA: An approach to distinguish true haplotypes from erroneous sequences
Authors: Tsuji Satsuki , Miya Masaki , Ushio Masayuki , Sato Hirotoshi , Minamoto Toshifumi , Yamanaka Hiroki
Published: September 2018

Recent advances in environmental DNA (eDNA) analysis using high-throughput sequencing (HTS) provide a non-invasive way to evaluate the intraspecific genetic diversity of aquatic macroorganisms. However, erroneous sequences present in HTS data can result in false positive haplotypes; therefore, reliable strategies are necessary to eliminate such erroneous sequences when evaluating intraspecific genetic diversity using eDNA metabarcoding. In this study, we propose an approach combining denoising using amplicon sequence variant (ASV) method and the removal of haplotypes with low detection rates. A mixture of rearing water of Ayu (Plecoglossus altivelis altivelis) was used as an eDNA sample. In total, nine haplotypes of Ayu mitochondrial D-loop region were contained in the sample and amplified by two-step tailed PCR. The 15 PCR replicates indexed different tags were prepared from the eDNA sample to compare the detection rates between true haplotypes and false positive haplotypes. All PCR replications were sequenced by HTS, and the total number of detected true haplotypes and false positive haplotypes were compared with and without denoising using the two types of ASV methods, Divisive Amplicon Denoising Algorithm 2 (DADA2) and UNOISE3. The use of both ASV methods considerably reduced the number of false positive haplotypes. Moreover, all true haplotypes were detected in all 15 PCR, whereas false positive haplotypes had detection rates varying from 1/15 to 15/15. Thus, by removing haplotypes with lower detection rates than 15/15, the number of false positive haplotypes were further reduced. The approach proposed in this study successfully eliminated most of false positive haplotypes in the HTS data obtained from eDNA samples, which allowed us to improve the detection accuracy for evaluating intraspecific genetic diversity using eDNA analysis.
Autoamplification and competition drive symmetry breaking: Initiation of centriole duplication by the PLK4-STIL network
Authors: Leda Marcin , Holland Andrew J. , Goryachev Andrew B.
Published: September 2018

Symmetry breaking, a central principle of physics, has been hailed as the driver of self-organization in biological systems in general and biogenesis of cellular organelles in particular, but the molecular mechanisms of symmetry breaking only begin to become understood. Centrioles, the structural cores of centrosomes and cilia, must duplicate every cell cycle to ensure their faithful inheritance through cellular divisions. Work in model organisms identified conserved proteins required for centriole duplication and found that altering their abundance affects centriole number. However, the biophysical principles that ensure that, under physiological conditions, only a single procentriole is produced on each mother centriole remain enigmatic. Here we propose a mechanistic biophysical model for the initiation of procentriole formation in mammalian cells. We posit that interactions between the master regulatory kinase PLK4 and its activator-substrate STIL form the basis of the procentriole initiation network. The model faithfully recapitulates the experimentally observed transition from PLK4 uniformly distributed around the mother centriole, the “ring”, to a unique PLK4 focus, the “spot”, that triggers the assembly of a new procentriole. This symmetry breaking requires a dual positive feedback based on autocatalytic activation of PLK4 and enhanced centriolar anchoring of PLK4-STIL complexes by phosphorylated STIL. We find that, contrary to previous proposals,in situdegradation of active PLK4 is insufficient to break symmetry. Instead, the model predicts that competition between transient PLK4 activity maxima for PLK4-STIL complexes explains both the instability of the PLK4 ring and formation of the unique PLK4 spot. In the model, strong competition at physiologically normal parameters robustly produces a single procentriole, while increasing overexpression of PLK4 and STIL weakens the competition and causes progressive addition of procentrioles in agreement with experimental observations.
Nasal respiration entrains neocortical long-range gamma coherence during wakefulness
Authors: Cavelli Matías , Castro-Zaballa Santiago , Gonzalez Joaquín , Rojas-Líbano Daniel , Rubido Nicolas , Velásquez Noelia , Torterolo Pablo
Published: September 2018

Recent studies have shown that slow cortical potentials in archi-, paleo- and neocortex, can phase-lock with nasal respiration. In some of these areas, gamma activity (γ: 30-100 Hz) is also coupled to the animal’s respiration. It has been hypothesized that this interaction plays a role in coordinating distributed neural activity. In a similar way, inter-cortical interactions at γ frequency has been also associated as a binding mechanism by which the brain generates temporary opportunities necessary for implementing cognitive functions. The aim of the present study is to explore if nasal respiration entrains inter-cortical interactions at γ frequency.

Six adult cats chronically prepared for electrographic recordings were employed in this study. Our results show that slow cortical respiratory potentials are present in several areas of the neocortex and olfactory bulb during wakefulness. Also, we found cross-frequency coupling between the respiratory phase and the amplitude of γ activity in all recorded areas. These oscillatory entrainments are independent of muscular activity, because are maintained during cataplexy induced by carbachol microinjection into the nucleus pontis oralis. Importantly, we observed that respiratory phase modulates the inter-cortical gamma coherence between neocortical pairs of electrodes during wakefulness. However, during NREM and REM sleep, breathing was unable to entrain the oscillatory activity, neither in the olfactory bulb nor in the neocortex. These results suggest a single unified phenomenon involving cross frequency coupling and long-range γ coherence across the neocortex. This fact could be related to a temporal binding process necessary for cognitive functions during wakefulness.
Identification of novel inhibitors of DLK palmitoylation by High Content Screening
Authors: Martin Dale D.O. , Kanuparthi Prasad S. , Holland Sabrina M. , Sanders Shaun S. , Jeong Hey-Kyeong , Einarson Marget B. , Jacobson Marlene , Thomas Gareth M.
Published: September 2018

After axonal insult and injury, Dual leucine-zipper kinase (DLK) conveys retrograde pro-degenerative signals to neuronal cell bodies via its downstream target c-Jun N-terminal kinase (JNK). We recently reported that such signals critically require modification of DLK by the fatty acid palmitate, via a process called palmitoylation. Compounds that inhibit DLK palmitoylation could thus reduce neurodegeneration, but identifying such inhibitors requires a suitable assay. Here we report that DLK subcellular localization in non-neuronal cells is highly palmitoylation-dependent and can be used as a proxy readout to identify inhibitors of DLK palmitoylation by High Content Screening (HCS). We exploited this highly specific localization of DLK-GFP as the basis for a screen of the Prestwick Compound Library™. We found that ketoconazole, a Prestwick Library compound that most dramatically affected DLK subcellular localization in our primary screen, inhibited DLK palmitoylation in a dose-dependent manner in follow-up biochemical assays. Moeroever, ketoconazole significantly blunted phosphorylation of c-Jun in primary sensory neurons subjected to Trophic Deprivation, a well known model of DLK-dependent pro-degenerative signaling. These findings suggest that our HCS platform is capable of identifying novel inhibitors of DLK palmitoylation and signalling that may have considerable therapeutic potential.
An oxide transport chain essential for balanced insulin signaling
Authors: Wu Xiangdong , Chen Keyang , Williams Kevin Jon
Published: September 2018

Patients with overnutrition, obesity, the atherometabolic syndrome, and type 2 diabetes mellitus exhibitimbalanced insulin action, also called pathway-selective insulin resistance. To control glycemia, they require hyperinsulinemia that then overdrives ERK and hepatic de-novo lipogenesis. We recently reported that NADPH oxidase-4 regulates balanced insulin action. Here, we show that NADPH oxidase-4 is part of a new limb of insulin signaling that we abbreviate “NSAPP” after its five major proteins. The NSAPP pathway is an oxide transport chain that begins when insulin stimulates NADPH oxidase-4 to generate. NADPH oxidase-4 handsto superoxide dismutase-3 for conversion into H2O2. The pathway ends when aquaporin-3 channels H2O2across the membrane to inactivate PTEN. Disruption of any component of the NSAPP chain, from NADPH oxidase-4 up to PTEN, leaves PTEN persistently active, thereby producing the same deadly pattern of imbalanced insulin action seen clinically. Unraveling the molecular basis for NSAPP dysfunction in overnutrition has now become a top priority.
Conserved mechanism of nucleoporin regulation of the Kcnq1ot1 imprinted domain with divergence in embryonic and trophoblast stem cells
Authors: Sachani Saqib S. , MacDonald William A. , Foulkrod Ashley M. , White Carlee R. , Zhang Liyue , Mann Mellissa R. W.
Published: September 2018

Genomic imprinting is an epigenetic phenomenon, whereby dual chromatin states lead to expression of one, and silencing of the other parental allele. Recently, we identified a nucleoporin-mediated mechanism of Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells by nucleoporins NUP107, NUP62 and NUP153. Here, we investigate their role in Kcnq1ot1 imprinted domain regulation in embryonic and trophoblast stem cells. Nucleoporin depletion in both lineages reduced Kcnq1ot1 noncoding RNA expression and volume, reduced Kcnq1ot1 paternal domain positioning at the nuclear periphery, and altered histone modifications along with histone modifier enrichment at the imprinting control region. However, while CTCF and cohesin were enriched at nucleoporin binding sites in the imprinting control region in embryonic stem cells, with reduction upon nucleoporin depletion, neither CTCF or cohesin occupied these sites in trophoblast stem cells. Finally, different subsets of silent paternal alleles were reactivated via altered histone modification upon nucleoporin depletion in embryonic and trophoblast stem cells. These results demonstrate a conserved mechanism with divergent regulation of the Kcnq1ot1 imprinted domain by NUP107, NUP62 and NUP153 in embryonic and extraembryonic lineages.

Summary Statement

Investigation of nucleoporins, NUP107, NUP62, and NUP153, revealed a conserved nucleoporin-dependent mechanism that mediates Kcnq1ot1 imprinted domain regulation in ES and TS cells, although notable lineage-specific divergence was also observed.
Dynamic network partnerships and social contagion drive cooperation
Authors: Dakin Roslyn , Ryder T. Brandt
Published: September 2018

Both reciprocity and positive assortment (like with like) are predicted to promote the evolution of cooperation, yet how partners influence each other’s behavior within dynamic networks is not well understood. One way to test this question is to partition phenotypic variation into differences among individuals in the expression of cooperative behavior (the “direct effect”), and plasticity within individuals in response to the social environment (the “indirect effect”). A positive correlation between these two sources of variation, such that more cooperative individuals elicit others to cooperate, is predicted to facilitate social contagion and selection on cooperative behavior. Testing this hypothesis is challenging, however, because it requires repeated measures of behavior across a dynamic social landscape. Here, we use an automated data-logging system to quantify the behavior of 179 wire-tailed manakins, birds that form cooperative male-male coalitions, and we use multiple-membership models to test the hypothesis that dynamic network partnerships shape within-individual variation in cooperative behavior. Our results show strong positive correlations between a bird’s own sociality and his estimated effect on his partners, consistent with the hypothesis that cooperation begets cooperation. These findings support the hypothesis that social contagion can facilitate selection for cooperative behavior within social networks.
High content analysis methods enable high throughput nematode discovery screening for viability and movement behavior in a multiplex sample in response to natural product treatment
Authors: Petitte Jennifer M. , Lewis Mary H. , Witsil Tucker K. , Huang Xiang , Rice John W.
Published: October 2018

Monitoring nematode parasite movement and mortality in response to various treatment samples usually involves tedious manual microscopic analysis. High Content Analysis instrumentation enables rapid and high throughput collecting of large numbers of treatment data on huge numbers of individual worms. These large sample sizes and increased sample diversity result in robust, reliable results with increased statistical significance. These methods would be applicable to relevant human, crop, or animal worm parasites.
Sequence data from the internal and external transcribed spacers of nuclear ribosomal DNA of Cyclamen purpurascens allow geographic mapping
Authors: Jaag Hannah Miriam
Published: October 2018

Cyclamen purpurascens (Alpine, European or purple cyclamen) is native to central Europe. Since decades it is discussed wether the occurrences of C. purpurascens north of the alps is native or if it was introduced. Here the nuclear ribosomal DNAs (rDNA) are sequenced in oder to obtain a phylogenetic geographic pattern. Phylogenetic analyses of ITS and NTS/ETS sequences distinguish three main clades coinciding with geographical distribution: Eastern alps (Austria), southern alps (Switzerland, Italy) and western Alps (France). The paper presents interspecific relationship of C. purpurascens based on geographic sequences of rDNA. The observed variations suggest that some plants were introduced via Benedictine gardens and the plants from Monastery gardens seem to origin from Lower Austria.
Pathways to balance mitochondrial translation and protein import
Authors: Priesnitz Chantal , Becker Thomas
Published: October 2018

Mitochondria contain their own genome that encodes for a small number of proteins, while the vast majority of mitochondrial proteins is produced on cytosolic ribosomes. The formation of respiratory chain complexes depends on the coordinated biogenesis of mitochondrially encoded and nuclear-encoded subunits. In this review, we describe pathways that adjust mitochondrial protein synthesis and import of nuclear-encoded subunits to the assembly of respiratory chain complexes. Furthermore, we outline how defects in protein import into mitochondria affect nuclear gene expression to maintain protein homeostasis under physiological and stress conditions.
Immunofluorescent Staining of Whole-Mount Mouse Embryos
Authors: Stewart Allison
Published: October 2018

Mouse embryos and fetal organs have no pigmentation except for the retinal pigmented epithelium of the eye at subsequent stages of development. This makes it difficult to visualize and photodocument embryonic structures using conventional light microscopy. This protocol is used to localize specific proteins in whole embryos or fetal organs using immunofluorescence. Various imaging modalities can then be used to visualize these expression patterns, for example, confocal microscopy or optical projection tomography.
Corporate governance structures and firm performance in large agriculture companies in New Zealand
Authors: Roudaki Jamal
Published: October 2018

Purpose

This study aims to explore the role of corporate governance (CG) characteristics on the financial performance of large agricultural companies in New Zealand. External auditor remuneration and board characteristics, such as board ownership, board compensation, board independence and board gender diversity, are addressed in the context of New Zealand’s agricultural companies by applying agency theory.

Design/methodology/approach

This paper uses a balanced panel data generalised least square regression analysis on 80 firm-years of observations over the period from 2012 to 2015.

Findings

Empirical analysis revealed that external auditors’ remuneration and board characteristics, such as board compensation and board independence, except for board ownership and board gender diversity, held no association with the agricultural companies’ performance. While board ownership and board gender diversity were negatively, but significantly, associated with firm performance, these results were pronounced in the listed agricultural companies rather than in the non-listed companies.

Research limitations/implications

This study encountered limitations commonly associated with the majority of industry-specific studies, i.e. small sample size and lack of published financial information from databases. Therefore, for generalisation, these limitations were considered relevant.

Practical implications

The results of this research project are beneficial for authorities and agricultural company directors in implementing CG principles and guidelines to empower such companies in international competition. Encouraging agricultural companies to maintain a high level of transparency in financial reporting is of central interest for the government’s economic development, and stock market investors achieve a high level of transparency in non-financial disclosures, the chief objective of this study. Finally, the results of this paper may encourage auditors to scrutinise CG disclosures by agricultural companies in more detail, looking for undisclosed information.

Social implications

The results of this paper may encourage managerial transparency by providing appropriate disclosures for the public benefit. Investors may benefit from the disclosure provided in their economic decision-making and the public may expand on the information disclosed in facilitating development through exports, expansion of foreign investments and the indigenous economy.

Originality/value

The findings contribute to the literature by providing novel and original insights into using a sample of listed and non-listed agricultural companies to extend the current understanding of the governance-performance nexus.
Influence of temperature and magnetic field on the oblique stagnation-point flow for a nanofluid past a vertical stretching/shrinking sheet
Authors: Borrelli Alessandra , Giantesio Giulia , Patria Maria Cristina , Roşca Natalia C. , Roşca Alin V. , Pop Ioan
Published: October 2018

Purpose

This paper aims to consider the influence of the temperature and of an external magnetic field on the steady oblique stagnation-point flow for a Boussinesquian nanofluid past a stretching or shrinking sheet.

Design/methodology/approach

The flow is reduced through similarity transformations to an ordinary boundary value problem, which is solved numerically in MATLAB using the bvp4c function. The behavior of the solution is discussed physically, and some analytical considerations concerning existence of the solution and the occurrence of dual solutions are drawn.

Findings

The study of the influence of an external magnetic field on the oblique stagnation-point flow of a Buongiorno's Boussinesquian nanofluid is carried out. The fluid clashes on a vertical stretching or shrinking sheet. Dual solutions appear for suitable values of the parameters.

Originality/value

The present results are new and original.
Forecasting performance of time series models on electricity spot markets
Authors: Gürtler Marc , Paulsen Thomas
Published: October 2018

Purpose

Study conditions of empirical publications on time series modeling and forecasting of electricity prices vary widely, making it difficult to generalize results. The key purpose of the present study is to offer a comparison of different model types and modeling conditions regarding their forecasting performance.

Design/methodology/approach

The authors analyze the forecasting performance of AR (autoregressive), MA (moving average), ARMA (autoregressive moving average) and GARCH (generalized autoregressive moving average) models with and without the explanatory variables, that is, power consumption and power generation from wind and solar. Additionally, the authors vary the detailed model specifications (choice of lag-terms) and transformations (using differenced time series or log-prices) of data and, thereby, obtain individual results from various perspectives. All analyses are conducted on rolling calibrating and testing time horizons between 2010 and 2014 on the German/Austrian electricity spot market.

Findings

The main result is that the best forecasts are generated by ARMAX models after spike preprocessing and differencing the data.

Originality/value

The present study extends the existing literature on electricity price forecasting by conducting a comprehensive analysis of the forecasting performance of different time series models under varying market conditions. The results of this study, in general, support the decision-making of electricity spot price modelers or forecasting tools regarding the choice of data transformation, segmentation and the specific model selection.