bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced processing and analysis of conventional confocal microscopy generated scanning FCS data
Authors: Waithe Dominic , Schneider Falk , Chojnacki Jakub , Clausen Mathias , Shrestha Dilip , de la Serna Jorge Bernardino , Eggeling Christian
Published: July 2017

Scanning Fluorescence Correlation Spectroscopy (scanning FCS) is a variant of conventional point FCS that allows molecular diffusion at multiple locations to be measured simultaneously. It enables disclosure of potential spatial heterogeneity in molecular diffusion dynamics and also the acquisition of a large amount of FCS data at the same time, providing large statistical accuracy. Here, we optimize the processing and analysis of these large-scale acquired sets of FCS data. On one hand we present FoCuS-scan, scanning FCS software that provides an end-to-end solution for processing and analysing scanning data acquired on commercial turnkey confocal systems. On the other hand, we provide a thorough characterisation of large-scale scanning FCS data over its intended time-scales and applications and propose a unique solution for the bias and variance observed when studying slowly diffusing species. Our manuscript enables researchers to straightforwardly utilise scanning FCS as a powerful technique for measuring diffusion across a broad range of physiologically relevant length scales without specialised hardware or expensive software.
A user’s guide to the online resources for data exploration, visualization, and discovery for the Pan-Cancer Analysis of Whole Genomes project (PCAWG)
Authors: Goldman Mary , Zhang Junjun , Fonseca Nuno A. , Cortés-Ciriano Isidro , Xiang Qian , Craft Brian , Piñeiro-Yáñez Elena , O’Connor Brian D , Bazant Wojciech , Barrera Elisabet , Muñoz-Pomer Alfonso , Petryszak Robert , Füllgrabe Anja , Al-Shahrour Fatima , Keays Maria , Haussler David , Weinstein John N. , Huber Wolfgang , Valencia Alfonso , Park Peter J. , Papatheodorou Irene , Zhu Jingchun , Ferretti Vincent , Vazquez Miguel ,   on behalf of the PCAWG Portals and Visualization Working Group,   the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: July 2017

The Pan-Cancer Analysis of Whole Genomes (PCAWG) project has generated, to our knowledge, the largest whole-genome cancer sequencing resource to date. Here we provide a user’s guide to the five publicly available online data exploration and visualization tools introduced in the PCAWG marker paper: The ICGC Data Portal, UCSC Xena, Expression Atlas, PCAWG-Scout, and Chromothripsis Explorer. We detail use cases and analyses for each tool, show how they incorporate outside resources from the larger genomics ecosystem, as well as demonstrate how the tools can be used together to more deeply understand tumor biology. Together, these tools enable researchers to dynamically query complex genomics data and integrate external information, enabling and enhancing PCAWG data interpretation. More information on these tools and their capabilities is available from The PCAWG Data Portals and Visualizations Page (http://docs.icgc.org/pcawg).
Temperature and Light Effects on Germination ofPeronospora effusaSporangia
Authors: Choudhury Robin Alan , McRoberts Neil
Published: July 2017

Spinach downy mildew, caused by the biotrophic oomycetePeronospora effusa, is an economically important disease that is found in all spinach growing regions of the US. To effectively predict disease risk we need to understand the response ofP. effusato different environmental conditions. We conducted several germination assays, exposingP. effusasporangia to different temperature and lighting conditions. Between 5 and 25°C under constant darkness, germination ofP. effusasporangia on water agar declined. These results were qualitatively different from a previous study ofP. effusagermination that found a bimodal response curve, with increased germination at lower and higher temperatures. Time course studies revealed that sporangia consistently germinated within the first twelve hours of plating, regardless of incubation temperature. Sporangia exposed to blue light had significantly reduced germination when compared with those exposed to red, yellow, or no light. Light intensity and color significantly impacted germination, although the effect of color varied by light intensity.
Chitosan membranes applied on the prostatic neurovascular bundles after nerve‐sparing robot‐assisted radical prostatectomy: a phase II study
Authors: Porpiglia Francesco , Bertolo Riccardo , Fiori Cristian , Manfredi Matteo , De Cillis Sabrina , Geuna Stefano
Published: July 2017

Objective

To evaluate the feasibility and the safety of applying chitosan membrane (ChiMe) on the neurovascular bundles (NVBs) after nerve‐sparing robot‐assisted radical prostatectomy (NS‐RARP). The secondary aim of the study was to report preliminary data and in particular potency recovery data.

Patients and Methods

This was a single‐centre, single‐arm prospective study, enrolling all patients with localised prostate cancer scheduled for RARP with five‐item version of the International Index of Erectile Function scores of >17, from July 2015 to September 2016. All patients underwent NS‐RARP with ChiMe applied on the NVBs. The demographics, perioperative, postoperative and complications data were evaluated. Potency recovery data were evaluated in particular and any sign/symptom of local allergy/intolerance to the ChiMe was recorded and evaluated.

Results

In all, 140 patients underwent NS‐RARP with ChiMe applied on the NVBs. Applying the ChiMe was easy in almost all the cases, and did not compromise the safety of the procedure. None of the patients reported signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging.

Conclusion

In our experience, ChiMe applied on the NVBs after NS‐RARP was feasible and safe, without compromising the duration, difficulty or complication rate of the ‘standard’ procedure. No patients had signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging. A comparative cohort would have added value to the study. The present paper was performed before Conformité Européene (CE)‐mark achievement.
Chronic spinal cord injury causes upregulation of serotonin (5‐HT)2A and 5‐HT2C receptors in lumbosacral cord motoneurons
Authors: Cao Nailong , Ni Jianshu , Wang Xiaohu , Tu Hongjian , Gu Baojun , Si Jiemin , Wu Gang , Andersson Karl‐Erik
Published: July 2017

Objectives

To investigate whether the voiding dysfunction caused by spinal cord injury (SCI) in rats can be improved by i.v. administration of the serotonin (5‐HT)2A/2C receptor agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropanehydrochloride (DOI), and to discuss whether the mechanism can be ascribed to 5‐HT2A and 5‐HT 2C receptor upregulation in lumbosacral cord motoneurons.

Materials and Methods

Female Sprague–Dawley rats were divided into two groups (SCI group vs normal control [NC] group). Under urethane anaesthesia, cystometry was performed to examine the variation in urodynamic variables before and after successive intrathecal (i.t.) administration of various doses of DOI into the lumbosacral cord. Changes in 5‐HT2A and ‐2C receptors in the lumbosacral cord were also investigated using immunohistochemical staining and Western blot analysis.

Results

Compared with NC rats, the SCI rats had higher bladder capacity and post‐void residual urine volume, and lower voiding efficiency. After SCI, DOI improved voiding efficiency, probably via external urethral sphincter (EUS) activity. Immunohistochemical staining and Western blot analysis showed that 5‐HT2A and ‐2C receptors were upregulated in lumbosacral cord motoneurons.

Conclusion

In rats with SCI, DOI can improve voiding efficiency; this may be attributable to 5‐HT2A and ‐2C receptor upregulation in lumbosacral cord motoneurons controlling EUS activity.
A brief psychological intervention for mothers of children with food allergy can change risk perception and reduce anxiety: Outcomes of a randomized controlled trial
Authors: Boyle R. J. , Umasunthar T. , Smith J. G. , Hanna H. , Procktor A. , Phillips K. , Pinto C. , Gore C. , Cox H. E. , Warner J. O. , Vickers B. , Hodes M.
Published: July 2017

Background

Mothers of children with food allergy have increased anxiety, which may be influenced by healthcare professionals’ communication of risk.

Objective

To evaluate a brief psychological intervention for reducing anxiety in mothers of children with food allergy.

Methods

Two hundred mothers of children with food allergy were recruited from allergy clinics. A computer‐generated randomization list was used to allocate participants to a single‐session cognitive behavioural therapy intervention including a risk communication module, or standard care. Anxiety and risk perception were assessed at 6 weeks and 1 year. Primary outcome was state anxiety at 6 weeks. Secondary outcomes included state anxiety at 1 year, risk perception at 6 weeks and 1 year, and salivary cortisol response to a simulated anaphylaxis scenario at 1 year.

Results

We found no significant difference in the primary outcome state anxiety at 6 weeks, with mean 31.9 (SD 10.2) intervention, 34.0 (10.2) control; mean difference 2.1 (95% CI −0.9, 5.0; P=.17). There was significantly reduced state anxiety at 6 weeks in the intervention group, in the subgroup of participants with moderate/high anxiety at enrolment (103/200, 52%), with mean 33.0 (SD 9.3) intervention, 37.8 (SD 10.0) control; mean difference 4.8 (95% CI 0.9, 8.7; P=.016; Cohen's d effect size 0.50). The psychological intervention also reduced risk perception and salivary cortisol response (P=.032; effect size 0.36).

Conclusion

We found evidence that a brief psychological intervention which incorporates accurate risk information may impact on anxiety, risk perception and physiological stress response in mothers of children with food allergy.
Pregnancy after laparoscopic ventral mesh rectopexy: implications and outcomes
Authors: Hogan A. M. , Tejedor P. , Lindsey I. , Jones O. , Hompes R. , Gorissen K. J. , Cunningham C.
Published: July 2017

Aim

Surgical management of rectal prolapse varies considerably. Most surgeons are reluctant to use ventral mesh rectopexy in young women until they have completed their family. The aim of the present study was to review outcomes of pregnancy following laparoscopic ventral mesh rectopexy from a tertiary referral centre over a 10‐year period (2006–2016) and to review the impact on pelvic floor symptoms.

Method

We undertook a retrospective review of a prospectively compiled database of patients who had undergone laparoscopic ventral rectopexy in a single centre over a 10‐year period. Pelvic floor symptom scores (Vaizey for incontinence and Longo for obstructive defaecation) were collected at initial presentation (pre‐intervention), post‐intervention and after child birth.

Results

In all, 954 rectopexies were performed over this 10‐year period. 225 (24%) patients were women and under 45 years of age (taken as an arbitrary cut‐off for decreased likelihood of pregnancy). Eight (4%) of these patients became pregnant following rectopexy. The interval between rectopexy and delivery was 42 months (21–50). Six patients delivered live babies by elective lower segment caesarean section and two by spontaneous vaginal delivery. Six were first babies and two were second. No mesh related adverse outcome was reported. No difference in pelvic floor symptoms was demonstrated on comparison of post‐rectopexy and post‐delivery scores.

Conclusion

This study provides the first description in the English language literature of safe delivery by elective lower segment caesarean section or spontaneous vaginal delivery following laparoscopic ventral mesh rectopexy. No adverse impact on pelvic floor related quality of life was detected.
Outcomes of patients diagnosed with acute myeloid leukemia after solid organ transplantation
Authors: Lontos Konstantinos , Agha Mounzer , Raptis Anastasios , Hou Jing‐Zhou , Farah Rafic , Redner Robert L. , Im Annie , Dorritie Kathleen A. , Sehgal Alison , Rossetti James , Saul Melissa , Gooding William E. , Humar Abhinav , Boyiadzis Michael
Published: July 2017

Organ transplant recipients are at an increased risk for subsequent cancer including acute myeloid leukemia (AML). Treatment of AML following solid transplantation represents a clinical challenge as most patients have significant comorbidities at the time of AML diagnosis. In this study, we evaluated the treatment and outcomes of patients who developed AML following solid organ transplantation at our institution and reviewed the literature on outcomes for these patients. The study cohort consisted of 14 patients (median age 66 years, range 52‐77 years) with newly diagnosed AML following solid organ transplantation. The median interval time between solid organ transplantation and AML diagnosis was 72 months (range 15‐368 months). Seven patients received standard induction chemotherapy, four patients received intermediate type therapy, and the remaining three patients were deemed not fit for therapy and received palliative and supportive care. Six of the 11 treated patients (55%) achieved complete remission (CR). The median overall survival (OS) for all patients was 6 months. The median OS for the patients who achieved complete remission after therapy was 17 months and 2 months for the remaining patients. Despite initial CR, relapse rates are still high, suggesting that alternative strategies for post‐remission therapies are warranted.
Accelerated kindling epileptogenesis in Tg4510 tau transgenic mice, but not in tau knockout mice
Authors: Liu Shijie , Shen Yu , Shultz Sandy R. , Nguyen Anne , Hovens Christopher , Adlard Paul A. , Bush Ashley I. , Chan Jianxiong , Kwan Patrick , O'Brien Terence J. , Jones Nigel C.
Published: July 2017

The biologic processes underlying epileptogenesis following a brain insult are not fully understood, but several lines of evidence suggest that hyperphosphorylation of tau may be an important factor in these processes. To provide further insight into the causal relationship between tau and epileptogenesis, this study applied amygdala kindling to rTg4510 mice that, concurrent with other pathologies, overexpress phosphorylated tau, tau knockout mice, or their respective wild‐type controls. Mice were electrically stimulated twice daily, 5 days per week for 3 weeks. Electroencephalography was recorded to measure the primary afterdischarge duration, and the behavioral progression of kindling‐induced seizures was assessed. rTg4510 mice (n = 10) had increased primary afterdischarge durations (p < 0.001), and significantly more rapid progression of kindling (p < 0.001), compared with wild‐type mice (n = 10). Tau knockout mice (n = 7), however, did not differ from their wild‐type counterparts (n = 8) on any of the seizure outcomes. These results suggest that Tg4510 mice are more vulnerable to epileptogenesis, but that the presence of tau itself is not necessary for kindling epileptogenesis to occur.
Effects of dobutamine, dopamine, phenylephrine and noradrenaline on systemic haemodynamics and intestinal perfusion in isoflurane anaesthetised horses
Authors: Dancker C. , Hopster K. , Rohn K. , Kästner S. B.
Published: July 2017

Background

In the horse, effects of cardiovascular‐active drugs on local perfusion of the gastrointestinal tract are poorly understood.

Objectives

To determine the effect of drugs commonly used to support blood pressure, on local intestinal blood flow and tissue oxygenation under isoflurane anaesthesia.

Study design

In vivorandomised crossover experiment.

Methods

Ten horses were anaesthetised with isoflurane. After 90 min of equilibration three doses (μg/kg bwt/min) of dobutamine (DOB0.5/1/3), dopamine (DA1/2/5), noradrenaline (NA0.1/0.2/0.5) and phenylephrine (PHE0.5/1/3) were infused for 15 min, in a randomised order, with a 45 min washout‐period. Blood flow and tissue oxygenation (sO2) of jejunum, colon and stomach were measured using white light remission spectrophotometry and laser doppler flowmetry; heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were measured and systemic vascular resistance (SVR) calculated.

Results

Compared to baseline high dose dobutamine significantly increasedCO,HR,MAP(P<0.001) and blood flow to the jejunum (+47 ± 26%, P = 0.001) and colon (+29 ± 15%, P<0.001) (mean ± s.d.). Dopamine (DA5) increasedCObut decreased colonic blood flow (−39 ± 21% from baseline, P<0.001), as well asSVRandMAPcompared to baseline (P<0.001). Noradrenaline had no significant influence on intestinal perfusion, but increasedMAPandSVRfrom baseline (P<0.001). Phenylephrine (PHE3) caused a significant decrease in blood flow andsO2, most profoundly at the colon compared to baseline (flow −44 ± 21%;sO2−16 ± 3%, P<0.001), whileMAPandSVRincreased andCOandHRdecreased (P<0.001).

Main limitations

The measurement technique only allows for flow measurements in arbitrary units, which can limit comparability to other techniques.

Conclusion

At the investigated doses dobutamine improved systemic and peripheral haemodynamics, while dopamine decreasedMAPand peripheral perfusion. Noradrenaline increasedMAPandSVRwhile peripheral blood flow was maintained, phenylephrine increasedMAP, but reduced both local and systemic perfusion.
Short frontal plane fractures involving the dorsoproximal articular surface of the proximal phalanx: Description of the injury and a technique for repair
Authors: Wright I. M. , Minshall G. J.
Published: July 2017

Background

Chip fractures of the dorsoproximal articular margin of the proximal phalanx are common injuries in racehorses. Large fractures can extend distal to the joint capsule insertion and have been described as dorsal frontal fractures.

Objectives

To report the location and morphology of short frontal plane fractures involving the dorsoproximal articular surface of the proximal phalanx and describe a technique for repair under arthroscopic and radiographic guidance.

Study design

Single centre retrospective case study.

Methods

Case records of horses with frontal plane fractures restricted to the dorsoproximal epiphysis and metaphysis of the proximal phalanx referred to Newmarket Equine Hospital were retrieved, images reviewed and lesion morphology described. A technique for repair and the results obtained are reported.

Results

A total of 22 fractures in 21 horses commencing at the proximal articular surface exited the dorsal cortex of the proximal phalanx distal to the metacarpophalangeal/metatarsophalangeal joint capsule in 17 hind‐ and five forelimbs. All were in Thoroughbred racehorses. In 16 cases these were acute racing or training injuries; 20 fractures were medial, one lateral and one was midline. All were repaired with a single lag screw using arthroscopic and radiographically determined landmarks. A total of 16 horses raced after surgery with performance data similar to their preinjury levels.

Main limitations

The study demonstrates substantial morphological similarities between individual lesions supporting a common pathophysiology, but does not identify precise causation. There are no cases managed differently that might permit assessment of the comparative efficacy of the treatment described.

Conclusions

Short frontal plane fractures involving the dorsoproximal margin of the proximal phalanx that exit the bone distal to the metacarpophalangeal/metatarsophalangeal joint capsule have substantial morphological similarities, are amenable to minimally invasive repair and carry a good prognosis for return to training and racing.
Projected climate changes threaten ancient refugia of kelp forests in the North Atlantic
Authors: Assis Jorge , Araújo Miguel B. , Serrão Ester A.
Published: July 2017

Intraspecific genetic variability is critical for species adaptation and evolution and yet it is generally overlooked in projections of the biological consequences of climate change. We ask whether ongoing climate changes can cause the loss of important gene pools from North Atlantic relict kelp forests that persisted over glacial–interglacial cycles. We use ecological niche modelling to predict genetic diversity hotspots for eight species of large brown algae with different thermal tolerances (Arctic to warm temperate), estimated as regions of persistence throughout the Last Glacial Maximum (20,000 YBP), the warmer Mid‐Holocene (6,000 YBP), and the present. Changes in the genetic diversity within ancient refugia were projected for the future (year 2100) under two contrasting climate change scenarios (RCP2.6 and RCP8.5). Models predicted distributions that matched empirical distributions in cross‐validation, and identified distinct refugia at the low latitude ranges, which largely coincide among species with similar ecological niches. Transferred models into the future projected polewards expansions and substantial range losses in lower latitudes, where richer gene pools are expected (in Nova Scotia and Iberia for cold affinity species and Gibraltar, Alboran, and Morocco for warm‐temperate species). These effects were projected for both scenarios but were intensified under the extreme RCP8.5 scenario, with the complete borealization (circum‐Arctic colonization) of kelp forests, the redistribution of the biogeographical transitional zones of the North Atlantic, and the erosion of global gene pools across all species. As the geographic distribution of genetic variability is unknown for most marine species, our results represent a baseline for identification of locations potentially rich in unique phylogeographic lineages that are also climatic relics in threat of disappearing.
Genetic mapping of biomass yield in three interconnected Miscanthus populations
Authors: Dong Hongxu , Liu Siyao , Clark Lindsay V. , Sharma Shailendra , Gifford Justin M. , Juvik John A. , Lipka Alexander E. , Sacks Erik J.
Published: July 2017

Improving biomass yield is a major goal of Miscanthus breeding. We conducted a study on one interspecific Miscanthus sinensis × Miscanthus sacchariflorus F1 population and two intraspecific M. sinensis F1 populations, each of which shared a common parent. A field trial was established at Urbana, IL during spring 2011, and phenotypic data were collected in 2012 and 2013 for fourteen yield traits. Six high‐density parental genetic maps, as well as a consensus genetic map integrating M. sinensis and M. sacchariflorus, were developed via the pseudotestcross strategy for noninbred parents with ≥1214 single‐nucleotide polymorphism markers generated from restriction site‐associated DNA sequencing. We confirmed for the first time a whole‐genome duplication in M. sacchariflorus relative to Sorghum bicolor, similar to that observed previously for M. sinensis. Four quantitative trait locus (QTL) analysis methods for detecting marker‐trait associations were compared: (1) individual parental map composite interval mapping analysis, (2) individual parental map stepwise analysis, (3) consensus map single‐population stepwise analysis and (4) consensus map joint‐population stepwise analysis. These four methods detected 288, 264, 133 and 109 total QTLs, which resolved into 157, 136, 106 and 86 meta‐QTLs based on QTL congruency, respectively, including a set of 59 meta‐QTLs common to all four analysis methods. Composite interval mapping and stepwise analysis co‐identified 118 meta‐QTLs across six parental maps, suggesting high reliability of stepwise regression in QTL detection. Joint‐population stepwise analysis yielded the highest resolution of QTLs compared to the other three methods across all meta‐QTLs. Strong, frequently advantageous transgressive segregation in the three populations indicated a promising future for breeding new higher‐yielding cultivars of Miscanthus.
The greenhouse gas intensity and potential biofuel production capacity of maize stover harvest in the US Midwest
Authors: Jones Curtis D. , Zhang Xuesong , Reddy Ashwan D. , Robertson G. Philip , Izaurralde Roberto César
Published: July 2017

Agricultural residues are important sources of feedstock for a cellulosic biofuels industry that is being developed to reduce greenhouse gas emissions and improve energy independence. While the US Midwest has been recognized as key to providing maize stover for meeting near‐term cellulosic biofuel production goals, there is uncertainty that such feedstocks can produce biofuels that meet federal cellulosic standards. Here, we conducted extensive site‐level calibration of the Environmental Policy Integrated Climate (EPIC) terrestrial ecosystems model and applied the model at high spatial resolution across the US Midwest to improve estimates of the maximum production potential and greenhouse gas emissions expected from continuous maize residue‐derived biofuels. A comparison of methodologies for calculating the soil carbon impacts of residue harvesting demonstrates the large impact of study duration, depth of soil considered, and inclusion of litter carbon in soil carbon change calculations on the estimated greenhouse gas intensity of maize stover‐derived biofuels. Using the most representative methodology for assessing long‐term residue harvesting impacts, we estimate that only 5.3 billion liters per year (bly) of ethanol, or 8.7% of the near‐term US cellulosic biofuel demand, could be met under common no‐till farming practices. However, appreciably more feedstock becomes available at modestly higher emissions levels, with potential for 89.0 bly of ethanol production meeting US advanced biofuel standards. Adjustments to management practices, such as adding cover crops to no‐till management, will be required to produce sufficient quantities of residue meeting the greenhouse gas emission reduction standard for cellulosic biofuels. Considering the rapid increase in residue availability with modest relaxations in GHG reduction level, it is expected that management practices with modest benefits to soil carbon would allow considerable expansion of potential cellulosic biofuel production.
Prevalence and significance of HMGA2 expression in oesophageal adenocarcinoma
Authors: Mito Jeffrey K , Agoston Agoston T , Dal Cin Paola , Srivastava Amitabh
Published: July 2017

Aims

Oesophageal adenocarcinoma (EAC) tumorigenesis has been linked primarily to loss‐of‐function mutations in tumour suppressor genes. Knowledge of specific oncogenes that drive tumour progression, and their relationship to outcomes, is limited. High mobility group AT‐hook 2 (HMGA2) has been reported to be amplified in a subset of EACs, but the clinicopathological and prognostic implications of HMGA2 expression in EAC are unknown.

Methods and results

We performed HMGA2 immunohistochemistry and fluorescence in‐situ hybridization (FISH) in EAC to determine its clinicopathological and prognostic significance. Ninety‐one primary EAC resections without neoadjuvant treatment were identified and immunohistochemistry for HMGA2 was performed. The presence or absence of nuclear staining was evaluated and correlated with predetermined clinicopathological parameters and patient outcomes. A selected subset of tumours was subjected to FISH to identify alterations at the HMGA2 locus. HMGA2 expression was present in 25 of 91 (27.4%) tumours. HMGA2‐expressing cells were present in solid, poorly differentiated areas of the tumours at the invasive front, or as single infiltrating cells. FISH showed that three to four copies of HMGA2 are frequently present in EAC irrespective of HMGA2 protein expression and that high level HMGA2 amplification is a rare event. HMGA2 expression was associated with numerous adverse clinicopathological parameters, including higher T‐ and N‐stage, the presence of lymphovascular invasion and with a worse recurrence‐free and overall survival.

Conclusion

Our data suggest that HMGA2 is regulated in EAC primarily through non‐chromosomal‐level alterations that lead to increased HMGA2 expression. HMGA2‐positive EAC correlates with adverse pathological features and worse patient outcomes.
A GRASP heuristic using path‐relinking and restarts for the Steiner traveling salesman problem
Authors: Interian Ruben , Ribeiro Celso C.
Published: July 2017

The traveling salesman problem (TSP) is one of the most studied problems in combinatorial optimization. Given a set of nodes and the distances between them, it consists in finding the shortest route that visits each node exactly once and returns to the first. Nevertheless, more flexible and applicable formulations of this problem exist and can be considered. The Steiner TSP (STSP) is a variant of the TSP that assumes that only a given subset of nodes must be visited by the shortest route, eventually visiting some nodes and edges more than once. In this paper, we adapt some classical TSP constructive heuristics and neighborhood structures to the STSP variant. In particular, we propose a reduced 2‐opt neighborhood and we show that it leads to better results in smaller computation times. Computational results with an implementation of a GRASP heuristic using path‐relinking and restarts are reported. In addition, ten large test instances are generated. All instances and their best‐known solutions are made available for download and benchmarking purposes.
Quality of life, anxiety prevalence, depression symptomatology and suicidal ideation among acne patients in Lithuania
Authors: Lukaviciute L. , Navickas P. , Navickas A. , Grigaitiene J. , Ganceviciene R. , Zouboulis C.C.
Published: July 2017

Background/Objective

We aimed to determine the prevalence of anxiety, depression symptomatology and suicidal ideation among patients with acne and the impact of this skin condition on the quality of life in Lithuania.

Methods

The mental health of patients with acne was assessed using an adapted Hospital Anxiety and Depression Scale, the Dermatology Quality of Life Index, questions about characteristics of acne. The study was authorized by the Regional Biomedical Research Ethics Committee.

Results

A total of 255 responders of 324 patients with acne included (84.4%) were assessed. 56.1% of the responders had comorbid anxiety, depression symptomatology or suicidal ideation related to acne. Among them, 38.4% had anxiety symptoms, 23.1% had depression symptoms and 12.9% had suicidal thoughts due to acne. About 96.5% of the responders had a reduced quality of life due to acne.

Conclusion

More than a half of the patients with acne who participated at the study had comorbid emotional disorders. Anxiety was the most prevalent sign, 1.7‐fold more prevalent than depression and threefold more prevalent than suicidal ideation. Depression was prevalent in more than every fourth responder and suicidal ideation afflicted every eighth acne patient. More than 90% of the patients had impaired life quality.
Preferential Plastid Retention by the Acquired Phototroph Mesodinium chamaeleon
Authors: Moeller Holly V. , Johnson Matthew D.
Published: July 2017

The ciliate genus Mesodinium contains species that rely to varying degrees on photosynthetic machinery stolen from cryptophyte algal prey. Prey specificity appears to scales inversely with this reliance: The predominantly phototrophic M. major/rubrum species complex exhibits high prey specificity, while the heterotrophic lineages M. pulex and pupula are generalists. Here, we test the hypothesis that the recently described mixotroph M. chamaeleon, which is phylogenetically intermediate between M. major/rubrum and M. pulex/pupula, exhibits intermediate prey preferences. Using a series of feeding and starvation experiments, we demonstrate that M. chamaeleon grazes and retains plastids at rates which often exceed those observed in M. rubrum, and retains plastids from at least five genera of cryptophyte algae. Despite this relative generality, M. chamaeleon exhibits distinct prey preferences, with higher plastid retention, mixotrophic growth rates and efficiencies, and starvation tolerance when offered Storeatula major, a cryptophyte that M. rubrum does not appear to ingest. These results suggest that niche partitioning between the two acquired phototrophs may be mediated by prey identity. M. chamaeleon appears to represent an intermediate step in the transition to strict reliance on acquired phototrophy, indicating that prey specificity may evolve alongside degree of phototrophy.
New Species of Spirotrichonympha from Reticulitermes and the Relationships Among Genera in Spirotrichonymphea (Parabasalia)
Authors: Gile Gillian H. , James Erick R. , Tai Vera , Harper James T. , Merrell Trevor L. , Boscaro Vittorio , Husník Filip , Scheffrahn Rudolf H. , Keeling Patrick J.
Published: July 2017

Spirotrichonymphea is a class of hypermastigote parabasalids defined by their spiral rows of many flagella. They are obligate hindgut symbionts of lower termites. Despite more than 100 yr of morphological and ultrastructural study, the group remains poorly characterised by molecular data and the phylogenetic positions and taxonomic validity of most genera remain in question. The genus Spirotrichonympha has been reported to inhabit several termite genera, including Reticulitermes, Coptotermes, and Hodotermopsis. The type species for this genus, Spirotrichonympha flagellata, was described from Reticulitermes lucifugus but no molecular data are yet available for this species. In this study, three new Spirotrichonympha species are described from three species of Reticulitermes. Their molecular phylogenetic position indicates that the genus is not monophyletic, as Spirotrichonympha species from Coptotermes, Paraneotermes, and Hodotermopsis branch separately. In contrast, the genus Holomastigotoides is monophyletic, as demonstrated using new sequences from Holomastigotoides species. The presence of Holomastigotoides in Prorhinotermes and the distinct phylogenetic positions of Spirotrichonympha from Reticulitermes and Coptotermes are consistent with a previously proposed symbiont fauna replacement in the ancestor of Reticulitermes.
A New Paradigm for Systematic Literature Reviews in Supply Chain Management
Authors: Durach Christian F. , Kembro Joakim , Wieland Andreas
Published: July 2017

While systematic literature reviews (SLRs) have contributed substantially to developing knowledge in fields such as medicine, they have made limited contributions to developing knowledge in the supply chain management domain. This is due to the ontological and epistemological idiosyncrasies of research in supply chain management, which need to be accounted for when retrieving, selecting, and synthesizing studies in an SLR. Therefore, we propose a new paradigm for SLRs in the supply chain domain that is based on both best practice and the unique attributes of doing supply chain management research. This approach involves exploring existing studies with attention to theoretical boundaries, units of analysis, sources of data, study contexts, and definitions and the operationalization of constructs, as well as research methods, with the goal of refining or revising existing theory. This new paradigm will push supply chain management research to the frontier of current methodological standards and build a foundation for improving the contribution of future SLRs in the supply chain and adjacent management disciplines.
Identification of EloR (Spr1851) as a regulator of cell elongation in Streptococcus pneumoniae
Authors: Stamsås Gro Anita , Straume Daniel , Ruud Winther Anja , Kjos Morten , Frantzen Cyril Alexander , Håvarstein Leiv Sigve
Published: July 2017

In a screen for mutations suppressing the lethal loss of PBP2b in Streptococcus pneumoniae we identified Spr1851 (named EloR), a cytoplasmic protein of unknown function whose inactivation removed the requirement for PBP2b as well as RodA. It follows from this that EloR and the two elongasome proteins must be part of the same functional network. This network also includes StkP, as this serine/threonine kinase phosphorylates EloR on threonine 89 (T89). We found that ΔeloR cells, and cells expressing the phosphoablative form of EloR (EloRT89A), are significantly shorter than wild‐type cells. Furthermore, the phosphomimetic form of EloR (EloRT89E) is not tolerated unless the cell in addition acquires a truncated MreC or non‐functional RodZ protein. By itself, truncation of MreC as well as inactivation of RodZ gives rise to less elongated cells, demonstrating that the stress exerted by the phosphomimetic form of EloR is relieved by suppressor mutations that reduce or abolish the activity of the elongasome. Of note, it was also found that loss of elongasome activity caused by truncation of MreC elicits increased StkP‐mediated phosphorylation of EloR. Together, the results support a model in which phosphorylation of EloR stimulates cell elongation, while dephosphorylation has an inhibitory effect.
GacS/GacA activates pyoluteorin biosynthesis through Gac/Rsm‐RsmE cascade and RsmA/RsmE‐driven feedback loop in Pseudomonas protegens H78
Authors: Wang Zheng , Huang Xianqing , Liu Yujie , Yang Guohuan , Liu Yang , Zhang Xuehong
Published: July 2017

The Gac/Rsm regulatory pathway in Pseudomonas spp. activates the production of various secondary metabolites, such as antibiotics, siderophores and exoenzymes. However, the biosynthesis of antifungal compound pyoluteorin (Plt) in Pseudomonas protegens H78 is almost entirely inhibited by double deletion of two csrA/rsmA family genes, namely, rsmA and rsmE. Here, we investigated the complicated regulatory mechanism of RsmA and RsmE in Plt biosynthesis in P. protegens H78. RsmE negatively regulated Plt biosynthesis and pltLABCDEFG expression by directly interacting with the mRNA leaders of pltR and pltAB. Conversely, the transcription of pltL‐G and pltR was positively influenced by RsmA through an uncharacterized mechanism. Further analyses demonstrated that pltL‐G expression was diminished in the rsmA/E mutant. The deficiency of pltL‐G expression in the gacA mutant was not reversed by any of the rsmA/E single or double mutations. The double deletion of rsmA/E reduced gacA expression by approximately 50% and almost completely inhibited the promoter activities of rsmXYZ sRNAs. The rsmY mutation significantly inhibited Plt biosynthesis. Taken together, GacS/GacA modulates Plt biosynthesis through two distinct pathways: Gac/Rsm‐RsmE traditional positive regulatory cascade and RsmA‐mediated positive transcriptional regulation. Moreover, a new positive feedback loop between RsmA/E and GacS/A‐RsmXYZ is essential for activating Plt biosynthesis.
Plant‐produced Zika virus envelope protein elicits neutralizing immune responses that correlate with protective immunity against Zika virus in mice
Authors: Yang Ming , Sun Haiyan , Lai Huafang , Hurtado Jonathan , Chen Qiang
Published: July 2017

The global Zika virus (ZIKV) outbreak and its link to foetal and newborn microcephaly and severe neurological complications in adults call for the urgent development of ZIKV vaccines. In response, we developed a subunit vaccine based on the ZIKV envelope (E) protein and investigated its immunogenicity in mice. Transient expression of ZIKV E (zE) resulted in its rapid accumulation in leaves of Nicotiana benthamiana plants. Biochemical analysis revealed that plant‐produced ZIKV E (PzE) exhibited specific binding to a panel of monoclonal antibodies that recognize various zE conformational epitopes. Furthermore, PzE can be purified to >90% homogeneity with a one‐step Ni2+ affinity chromatography process. PzE are found to be highly immunogenic, as two doses of PzE elicited both potent zE‐specific antibody and cellular immune responses in mice. The delivery of PzE with alum induced a mixed Th1/Th2 immune response, as the antigen‐specific IgG isotypes were a mixture of high levels of IgG1/IgG2c and splenocyte cultures from immunized mice secreted significant levels of IFN‐gamma, IL‐4 and IL‐6. Most importantly, the titres of zE‐specific and neutralizing antibodies exceeded the threshold that correlates with protective immunity against multiple strains of ZIKV. Thus, our results demonstrated the feasibility of plant‐produced ZIKV protein antigen as effective, safe and affordable vaccines against ZIKV.
Early Life UV and Risk of Basal and Squamous Cell Carcinoma in New South Wales, Australia
Authors: Kricker Anne , Weber Marianne , Sitas Freddy , Banks Emily , Rahman Bayzidur , Goumas Chris , Kabir Ahsanul , Hodgkinson Verity S. , van Kemenade Cathelijne H. , Waterboer Tim , Armstrong Bruce K.
Published: July 2017

Sun exposure is the main cause of squamous (SCC) and basal cell carcinoma (BCC) although pattern and amount differ by cancer type, and sun sensitivity is the major host risk factor. Our study investigated risk factors and residential ambient UV in a population‐based sample of Australian 45 and Up Study participants: 916 BCC cases, 433 SCC cases, 1224 controls. Unconditional logistic regression models adjusting for key covariates demonstrated 60% increased BCC risk and two‐fold increased SCC risk with sun sensitivity, and three‐ and four‐fold increased risk, respectively, with solar keratoses. BCC but not SCC risk increased with higher early‐life residential UV in all participants (odds ratio (OR) = 1.54; 95% CI 1.22–1.96 for intermediate; OR = 1.31; 95% CI 1.03–1.68 for high UV at birthplace) and similarly in Australian‐born participants (P‐values < 0.05). Risk of SCC but not BCC increased with long‐term cumulative sun exposure assessed by self‐reported outdoor work (OR 1.74, 95% CI 1.21–2.49). In conclusion, sun sensitivity is important for both cancers, early‐life UV but not cumulative UV appears to increase BCC risk, the former an apparently novel finding, and SCC risk appears only to be related to long‐term cumulative sun exposure.
Distinct properties of the triplet pair state from singlet fission
Authors: Trinh M. Tuan , Pinkard Andrew , Pun Andrew B. , Sanders Samuel N. , Kumarasamy Elango , Sfeir Matthew Y. , Campos Luis M. , Roy Xavier , Zhu X.-Y.
Published: July 2017

The triplet pair from singlet fission is characterized by distinct spectroscopic signature and can be difficult to break apart.
Increased Processivity, Misincorporation, and Nucleotide Incorporation Efficiency in Sulfolobus solfataricus Dpo4 Thumb Domain Mutants
Authors: Wang Li , Liang Chenchen , Wu Jing , Liu Liming , Tyo Keith E. J.
Published: July 2017

The present study aimed to increase the processivity of
Sulfolobus solfataricus
DNA polymerase Dpo4. Protein engineering and bioinformatics were used to compile a library of potential Dpo4 mutation sites. Ten potential mutants were identified and constructed. A primer extension assay was used to evaluate the processivity of Dpo4 mutants. Thumb (A181D) and finger (E63K) domain mutants showed a processivity of 20 and 19 nucleotides (nt), respectively. A little finger domain mutant (I248Y) exhibited a processivity of 17 nt, only 1 nt more than wild-type Dpo4. Furthermore, the A181D mutant showed lower fidelity and higher nucleotide incorporation efficiency (4.74 × 10
−4
s
−1
μM
−1
) than E63K and I248Y mutants. When tasked with bypassing damage, the A181D mutant exhibited a 3.81-fold and 2.62-fold higher catalytic efficiency (
k
cat
/

K
m

) at incorporating dCTP and dATP, respectively, than wild-type Dpo4. It also showed a 55% and 91.5% higher catalytic efficiency when moving beyond the damaged 8-oxoG:C and 8-oxoG:A base pairs, respectively, compared to wild-type Dpo4. Protein engineering and bioinformatics methods can effectively increase the processivity and translesion synthesis ability of Dpo4.

IMPORTANCE
DNA polymerases with poor fidelity can be exploited to store data and record changes in response to the intracellular environment.
Sulfolobus solfataricus
Dpo4 is such an enzyme, although its use is hindered by its low processivity. In this work, we used a bioinformatics and protein engineering approach to generate Dpo4 mutants with improved processivity. We identified the Dpo4 thumb domain as the most relevant in controlling processivity.
Effect of interdisciplinary care on weight loss: a randomised controlled trial
Authors: Tapsell Linda C , Lonergan Maureen , Batterham Marijka J , Neale Elizabeth P , Martin Allison , Thorne Rebecca , Deane Frank , Peoples Gregory
Published: July 2017

Objective

To determine the effectiveness of a novel interdisciplinary treatment compared with usual care on weight loss in overweight and obese adult volunteers.

Design

Single blinded controlled trial. Participants randomly assigned to usual care (C, general guideline-based diet and exercise advice), intervention (I, interdisciplinary protocol) or intervention + a healthy food supplement (30 g walnuts/day) (IW).

Setting

Community based study, Illawarra region, south of Sydney, Australia.

Participants

Generally well volunteer adult residents, 25-54 years, body mass index (BMI) 25-40kg/m2were eligible. At baseline 439 were assessed, 377 were randomised, 298 completed the 3-month intensive phase and 178 completed the 12-month follow-up.

Interventions

Treatment was provided at clinic visits intensively (0 months, 1 month, 2 months, 3 months) then quarterly to 12 months. Support phone calls were quarterly. All participants underwent blinded assessments for diet, exercise and psychological status.

Primary and secondary measures

The primary outcome was difference in weight loss between baseline and 12 months (clinically relevant target 5% loss). Secondary outcomes were changes in blood pressure, fasting blood glucose and lipids, and changes in diet, exercise and psychological parameters.

Results

At 12 months, differences in weight loss were identified (p<0.001). The I group lost more than controls at 3 months (91.11 (92.23,90.00), p<0.05) and the IW more than controls at 3 months (91.25 (92.35,90.15), p<0.05) and 6 months (92.20 (93.90,90.49), p<0.01). The proportion achieving 5% weight loss was significantly different at 3 months, 6 months and 9 months (p=0.04, p=0.03, p=0.03), due to fewer controls on target at 3 months, 6 months and 9 months and more IW participants at 6 months. Reductions in secondary outcomes (systolic blood pressure, blood glucose/lipid parameters and lifestyle measures) followed the pattern of weight loss.

Conclusions

An interdisciplinary intervention produced greater and more clinically significant and sustained weight loss compared with usual care. The intensive phase was sufficient to reach clinically relevant targets, but long-term management plans may be required.

Trial registration number

ANZCTRN 12614000581662; Post-results.