bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost‐effective approach to the diagnostic workup of B cell lymphoproliferative disorders via optimal integration of flow cytometric data
Authors: Mason E. F. , Morgan E. A. , Pinkus G. S. , Pozdnyakova O.
Published: January 2017

Introduction

The workup of lymphoproliferative disorders (LPDs) involves the combined use of flow cytometry (FC) and immunohistochemistry (IHC). This often results in duplicate immunophenotypic testing and adds costs that may not be eligible for reimbursement based on the Medicare National Correct Coding Initiative. We aimed to establish a cost‐effective diagnostic algorithm based on initial FC categorization to reduce repetitive immunophenotyping.

Methods

We retrospectively reviewed 242 cases of suspected LPDs with concurrent FC and IHC testing over a 12‐month period. We correlated FC with surgical diagnoses and evaluated the frequency of repeat IHC testing.

Results

Repetitive immunophenotyping was common; overall, 85% of cases had at least one marker repeated. Concordant cases were significantly less likely to have markers repeated than discordant cases. Of concordant B cell malignancies, 57% represented recurrent disease; however, repeat marker usage was not decreased as compared to new diagnoses. The most frequently repeated markers were CD3, CD5, CD10, and CD20.

Conclusions

We propose that in concordant cases, CD5 and CD10 should not be repeated by IHC; this would decrease the use of these markers by 80% and 76%, respectively. We developed an algorithmic approach to IHC usage that has improved incorporation of FC data at our institution and may reduce healthcare costs.
Development of a novel automated screening method for detection of FVIII Inhibitors
Authors: Evans M. S. , Donaldson K. J. , Eyster M. E.
Published: January 2017

Introduction

Factor VIII activity is routinely determined by measuring the activated partial thromboplastin time (aPTT) of a patient plasma sample and determining percent activity from a standard curve. To maximize the detection of a clotting factor inhibitor, a subjective assessment of parallelism of a patient curve compared with a standard curve is performed. We developed and validated an automated objective method to assess parallelism as a rapid screening tool for detection of an inhibitor to factor VIII during routine FVIII assays.

Methods

We performed FVIII assays on a subset of FVIII‐deficient patients with hemophilia A with and without inhibitors. Utilizing a ratio of the slopes from parallelism curves obtained by an independent Microsoft excel program in patients compared with a normal standard curve, we determined a cutoff ratio predictive for presence of an inhibitor.

Results

A cutoff ratio of patient to control slopes of <0.45 for the detection of an inhibitor to FVIII was 100% sensitive and 91.6% specific, with a positive predictive value of 92.3% and a negative predictive value of 100%.

Conclusion

Utilizing a ratio of the slopes from parallelism curves in patients with and without an inhibitor, we developed and validated a rapid, automated, and objective method to assess parallelism as an added screening tool for detection of an inhibitor to factor VIII during routine FVIII assays on a STAGO‐based coagulation platform. This simple automated method has the potential to detect inhibitors to other clotting factors.
Host controls of HIV broadly neutralizing antibody development
Authors: Kelsoe Garnett , Haynes Barton F.
Published: January 2017

Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been made recently in understanding host immunologic controls of bNAb induction and maturation in the setting of HIV infection, and point to key roles for both central and peripheral immunologic tolerance mechanisms in limiting bnAb development. Immune tolerance checkpoint inhibition has been transformative in promotion of anti‐tumor CD8 T‐cell responses in the treatment of certain malignancies. Here, we review the evidence for host controls of bNAb responses, and discuss strategies for the transient modulation of immune responses with vaccines toward the goal of enhancing germinal center B‐cell responses to favor bNAb B‐cell lineages and to foster their maturation to full neutralization potency.
Tfh cells and HIV bnAbs, an immunodominance model of the HIV neutralizing antibody generation problem
Authors: Havenar‐Daughton Colin , Lee Jeong Hyun , Crotty Shane
Published: January 2017

The generation of HIV bnAbs may be one of the greatest feats of the human immune system and our best hope of finally creating an HIV vaccine. The striking amount of somatic hypermutation in HIV bnAbs led to the hypothesis that T follicular helper (Tfh) cells and germinal centers (GC) play a critical role in the ability of the immune system to generate these uncommon antibodies. In this review, we first summarize what is known about the immunological process of HIV bnAb development, the challenges of eliciting bnAbs via immunizations, and the putative central roles of Tfh cells and GC in the generation of HIV bnAbs. Next, we explore factors that have impeded our understanding of the GC and Tfh‐cell processes involved in bnAb generation, including the difficulty of quantifying antigen‐specific GC Tfh cells and the difficulty of tracking GC in human and non‐human primate vaccine studies. Finally, we discuss antibody immunodominance pertaining to neutralizing antibody generation and the GC response, propose models to explain the negative effects of immunodominance on neutralizing antibody generation, and consider means of optimizing Tfh and GC responses to potentially overcome these problems.
The modeling of time to enterotoxin detection of Staphylococcus aureus in chicken meat
Authors: Chaves Rafael D. , Silva Alessandra R. , Alvarenga Verônica O. , Pereira José L. , Mousavi Khaneghah Amin
Published: January 2017

This study was aimed to model the Time to Enterotoxin Detection (TED) in chicken meat as a function of temperature and salt concentration (NaCl) using a polynomial response surface model. The standard strain of Staphylococcus (ATCC 13565) as the producer of enterotoxin A producer was inoculated into 25 g of chicken meat sample. The samples were prepared according to proposed combinations of NaCl concentration, pH, and temperature with consider to the experimental design. At intervals of time, (1–24 hours), the approved enterotoxin extraction protocol and Staphylococcal Enterotoxin (SE) detection techniques (mini VIDAS, BioMérieux) were applied. Four hours was determined as the lowest detection time among the experiments at 37 and 41 °C treated with 0.8 or 1% and 1% salt, respectively. Following the linear and quadratic temperature patterns, the temperature often found in kitchen (tropical countries) is able to reduce TED even in high concentrations of salt.

Practical applications

The proposed models could be applied to calculate the Time to Enterotoxin Detection (TED) in similar chicken meat products with consider to defined variables. An acceptable prediction for TED (R2 = 0.83, bias = 0.81) was provided by the established model as the result of variations in salt concentration and temperature. Hence, the introduced model can be approached to guaranty the proposed level of food safety.
Patient Needs and Environments for Cancer Infusion Treatment
Authors: Wang Zhe , Pukszta Michael
Published: January 2017

More than 50% of cancer patients receive chemotherapy by infusion, which is typically delivered in ambulatory healthcare settings. Influences of the built environment on inpatient care are well documented, but environmental research focusing on ambulatory healthcare is lacking. This empirical research focuses on cancer infusion environments and reveals important patient needs linking the built environment to infusion care. A survey of 166 patients and observations of 252 patients were conducted in an academic cancer center to explore patient preferences on private, semiopen, or open environments for infusion treatment and the reasons for their preferences. The observations investigated patient interactions with the environments during infusion treatment. Findings from qualitative and quantitative data analyses showed that private, semiopen, or open spaces were generally equally popular among patient participants. Needs for high–level privacy, quiet places to nap or sleep, social interaction, patient–nurse access, sunshine, and views to the outside were identified as major reasons for patient preferences. Items important to patients during treatment included patient chair tablets, guest chairs, personal televisions, nap blankets, food or beverages, window views, and sunshine. Participants with access to positive window views reported significantly lower levels of stress and greater hope for successful treatment than their counterparts ( p < .05). Findings suggest that important environmental features of ambulatory healthcare settings are both similar to and different from that of inpatient environments in the way they significantly impact the quality and experience of care.
DNA ploidy and cell cycle protein expression in oral squamous cell carcinomas with and without lymph node metastases
Authors: Zargoun Ibtisam M. , Bingle L. , Speight P. M.
Published: January 2017

Background

Oral squamous cell carcinoma (OSCC) is the most frequently occurring malignant tumour in the oral cavity. OSCC arises because of multiple genetic alterations. Cell cycle aberrations and aneuploidy are reportedly among the main characteristics of cancer cells and are associated with aggressive growth and poor prognosis.

Methods

The study sample included 47 non‐metastasised and 39 metastasised primary OSCC, with matched positive cervical lymph nodes and 17 normal oral mucosa samples. Tissue microarrays (TMAs) were prepared with a minimum of three cores from each case. TMA sections were cut and immunostained with MCM2, Ki‐67, geminin and cyclin D1 antibodies. DNA image analysis was performed on the whole tissue section before TMAs were created.

Results

The results revealed that there were no differences in cell cycle protein expression in different areas of the tumours or between the metastatic and non‐metastatic carcinomas. None of the cell cycle proteins showed significant differences between the lymph node metastasis and the primary OSCC, except for Ki‐67. Geminin/Ki‐67 ratio showed significant difference between metastatic and non‐metastatic tumours. Aneuploidy was detected in all (100%) cases of OSCC. Similarly, all lymph node samples (39 cases) were aneuploid.

Conclusion

The results suggest that although there was dysregulation of cell cycle regulatory proteins, only Ki‐67 and the MCM2/Ki‐67 and geminin/Ki‐67 ratios may have prognostic significance in oral cancer. DNA ploidy alone was not specific and may not be a good tool to evaluate prognosis or metastatic progression in oral cavity carcinomas.
Fucosterol, isolated from Ecklonia stolonifera, inhibits adipogenesis through modulation of FoxO1 pathway in 3T3-L1 adipocytes
Authors: Lee Ji-Hyun , Jung Hyun Ah , Kang Min Jae , Choi Jae Sue , Kim Gun-Do
Published: January 2017

Objectives

The purpose of this study was to investigate the effects of fucosterol on adipogenesis of 3T3-L1 preadipocytes and its underlying mechanisms.

Methods

Fucosterol, isolated from brown algae, Ecklonia stolonifera. We investigated the levels of lipid accumulation using Oil Red O staining. We conducted Western blot analysis to investigate regulatory effects of fucosterol on expression of phosphoinositide 3-kinase (PI3K), Akt, extracellular signal-regulated kinase (ERK), forkhead box protein O 1 (FoxO1) in 3T3-L1 adipocytes.

Key findings

Fucosterol significantly reduced intracellular lipid accumulation of 3T3-L1 adipocytes at concentrations of 25 and 50 μm. Fucosterol downregulated insulin-triggered PI3K/Akt, and ERK pathways. It subsequently decreased expression of adipogenic transcription factors, including PPARγ, C/EBPα and SREBP-1. In addition, fucosterol enhanced SirT1 expression while decreased phospho-FoxO1 expression which resulted in the activation of FoxO1.

Conclusions

We revealed that fucosterol inhibited adipogenesis of 3T3-L1 preadipocytes through modulation of FoxO signalling pathway. Therefore, our results suggest that fucosterol may be used for novel agents for the treatment of obesity.
In-vitro and in-vivo evaluation of the modulatory effects of the multitarget compound ASS234 on the monoaminergic system
Authors: Esteban Gerard , Van Schoors Jolien , Sun Ping , Van Eeckhaut Ann , Marco-Contelles José , Smolders Ilse , Unzeta Mercedes
Published: January 2017

Objectives

To evaluate the in-vitro and in-vivo effects on monoaminergic neurotransmission of ASS234, a promising multitarget-directed ligand (MTDL), for Alzheimer's disease (AD) therapy.

Methods

In vitro was explored the effect of ASS234 on the monoaminergic metabolism in SH-SY5Y and PC12 cell lines, and remaining activity of both monoamine oxidase (MAO) isoforms was assessed. The corresponding dopamine (DA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) and noradrenaline (NA) levels were determined by HPLC-ED. In-vivo experiments were carried out Wistar rats and intracerebral guide cannulas were implanted in the hippocampus and in the prefrontal cortex by sterotaxic coordinates. The day after microdialysis samples were collected and levels of 5-HT, DA and NA were determined by (UHPLC) with electrochemical detector.

Key findings

ASS234 induced a significant increase in serotonin (5-HT) levels in SH-SY5Y cells. In PC12 cells, ASS234 increased significantly the ratio of dopamine (DA)/(HVA + DOPAC), although no apparent differences in (NA) were observed. By in-vivo microdialysis, ASS234 showed a significant increase in the extracellular levels of 5-HT and NA in hippocampus whereas in the prefrontal cortex, DA and NA also increased significantly.

Conclusions

This study reveals the ability of ASS234 a MTDL compound, to enhance the monoaminergic neurotransmission supporting its potential use in AD therapy.
Dietary inclusion of tomato pomace improves meat oxidative stability of young pigs
Authors: Correia C. S. , Alfaia C. M. , Madeira M. S. , Lopes P. A. , Matos T. J. S. , Cunha L. F. , Prates J. A. M. , Freire J. P. B.
Published: January 2017

The aim of this study was to assess the nutritional effect of tomato pomace, in combination with two distinct fat sources (lard or soya bean oil), on longissimus lumborum muscle, subcutaneous fat and liver of young pigs. Forty male pigs of 4 weeks old were randomly assigned to four dietary treatments using two fibre sources (wheat bran or 5.0% tomato pomace) and two fat sources (lard or soya bean oil), in a 2 × 2 factorial design for a 5‐week trial. Tomato pomace did not improve colour, fatty acid profile, cholesterol content or lipid oxidation, nor did it yield detectable levels in lycopene or β‐carotene in the meat (p > 0.05). However, a positive increase in α‐tocopherol content of meat and liver was observed in pigs fed tomato pomace (p < 0.05). Compared with lard, soya bean oil increased MUFA and PUFA proportions and decreased the percentage of SFA (p < 0.05). Our results indicate that 5.0% of tomato pomace increases pork oxidative stability and that 5.0% of soya bean oil, compared with lard, improves its nutritional quality.
Shift in disparities in hepatitis C treatment from interferon to DAA era: A population‐based cohort study
Authors: Janjua N. Z. , Islam N. , Wong J. , Yoshida E. M. , Ramji A. , Samji H. , Butt Z. A. , Chong M. , Cook D. , Alvarez M. , Darvishian M. , Tyndall M. , Krajden M.
Published: January 2017

We evaluated the shift in the characteristics of people who received interferon‐based hepatitis C virus (HCV) treatments and those who received recently introduced direct‐acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon‐based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon‐free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon‐free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon‐based treatment, people with HIV co‐infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31‐3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45‐2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31‐2.28), diabetes (aOR: 1.30, 95% CI: 1.10‐1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09‐1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01‐1.67) were more likely to receive interferon‐free DAAs. Socio‐economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58‐0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV‐co‐infected), although gaps remain for the socio‐economically marginalized populations.
Determination of cloxacillin residues in dairy cows after intramammary administration
Authors: Burmańczuk A. , Grabowski T. , Osypiuk M. , Polska B. , Kowalski C.
Published: January 2017

The aim of this study was to perform a comparative analysis of the characteristics of cloxacillin (CLO) (MRL of withdrawal in bovine milk is 30 ng/g) after a single intramammary (IMM) dose in the dry period (DP) and lactation (LP), and to establish a high‐performance liquid chromatography (HPLC) analytical method for CLO detection in milk. The research was conducted on a group of 10 cows in DP and 10 in LP. A single dose of 600 mg of CLO was administrated by the IMM route for a single quarter in DP and 500 mg for a single quarter in LP. CLO concentration was analyzed by HPLC. CLO was monitored at a wavelength of 206 nm. Pharmacokinetic calculations were performed using Phoenix® WinNonlin® 6.4 software. The calibration curve was linear over the range of 13.03–28 019.00 ng/g with the coefficient of determination R2 > 0.999. CLO withdrawal in both the LP and DP group had a biphasic nature. The total CLO elimination in the DP and LP group was reached after 36 and 6.5 days, respectively. A quantitative and confirmatory method for the determination of CLO in fresh milk has been established. We have confirmed that the withdrawal of CLO in the DP group is not a linear process and has a stepwise character.
Incipient speciation driven by hypertrophied lips in Midas cichlid fishes?
Authors: Machado‐Schiaffino Gonzalo , Kautt Andreas F. , Torres‐Dowdall Julian , Baumgarten Lukas , Henning Frederico , Meyer Axel
Published: January 2017

Sympatric speciation has been debated in evolutionary biology for decades. Although it has gained in acceptance recently, still only a handful of empirical examples are seen as valid (e.g. crater lake cichlids). In this study, we disentangle the role of hypertrophied lips in the repeated adaptive radiations of Nicaraguan crater lake cichlid fish. We assessed the role of disruptive selection and assortative mating during the early stages of divergence and found a functional trade‐off in feeding behaviour between thick‐ and thin‐lipped ecotypes, suggesting that this trait is a target of disruptive selection. Thick‐lipped fish perform better on nonevasive prey at the cost of a poorer performance on evasive prey. Using enclosures in the wild, we found that thick‐lipped fish perform significantly better in rocky than in sandy habitats. We found almost no mixed pairs during two breeding seasons and hence significant assortative mating. Genetic differentiation between ecotypes seems to be related to the time since colonization, being subtle in L. Masaya (1600 generations ago) and absent in the younger L. Apoyeque (<600 generations ago). Genome‐wide differentiation between ecotypes was higher in the old source lakes than in the young crater lakes. Our results suggest that hypertrophied lips might be promoting incipient sympatric speciation through divergent selection (ecological divergence in feeding performance) and nonrandom mating (assortative mating) in the young Nicaraguan crater lakes. Nonetheless, further manipulative experiments are needed in order to confirm the role of hypertrophied lips as the main cue for assortative mating.
Nonindependence and sensitivity analyses in ecological and evolutionary meta‐analyses
Authors: Noble Daniel W.A. , Lagisz Malgorzata , O'dea Rose E. , Nakagawa Shinichi
Published: January 2017

Meta‐analysis is an important tool for synthesizing research on a variety of topics in ecology and evolution, including molecular ecology, but can be susceptible to nonindependence. Nonindependence can affect two major interrelated components of a meta‐analysis: (i) the calculation of effect size statistics and (ii) the estimation of overall meta‐analytic estimates and their uncertainty. While some solutions to nonindependence exist at the statistical analysis stages, there is little advice on what to do when complex analyses are not possible, or when studies with nonindependent experimental designs exist in the data. Here we argue that exploring the effects of procedural decisions in a meta‐analysis (e.g. inclusion of different quality data, choice of effect size) and statistical assumptions (e.g. assuming no phylogenetic covariance) using sensitivity analyses are extremely important in assessing the impact of nonindependence. Sensitivity analyses can provide greater confidence in results and highlight important limitations of empirical work (e.g. impact of study design on overall effects). Despite their importance, sensitivity analyses are seldom applied to problems of nonindependence. To encourage better practice for dealing with nonindependence in meta‐analytic studies, we present accessible examples demonstrating the impact that ignoring nonindependence can have on meta‐analytic estimates. We also provide pragmatic solutions for dealing with nonindependent study designs, and for analysing dependent effect sizes. Additionally, we offer reporting guidelines that will facilitate disclosure of the sources of nonindependence in meta‐analyses, leading to greater transparency and more robust conclusions.
Investigating Language Tutor Social Inclusion Identities
Authors: Barkhuizen Gary
Published: January 2017

This article explores the identities of tutors working in one‐to‐one instructional arrangements, which entail a tutor and an adult English learner working together to meet the particular language learning needs and goals of the learner. The tutors in this study are matched with their partners through an organization in New Zealand which aims to provide a community‐based service that supports settlement for immigrants and refugees through English. The findings are presented through an analysis of a series of ‘short stories,’ short excerpts of data extracted from a larger set of interviews with the tutors. They are analyzed thematically for their content. In making sense of the content, attention is necessarily paid to the narrators’ orientation within micro, meso, and macro spatial and temporal contexts; stories, Stories, and STORIES. Specifically, the tutors’ identities are examined as social inclusion tutor identities; that is, identity is conceptualized narratively as co‐constructed and situated in the (short) stories they tell about their lived and imagined tutoring social inclusion experiences. In the case of these tutors, their experiences include primarily and intimately the lives of their refugee and immigrant English learners.
The parthenocarpic hydra mutant reveals a new function for a SPOROCYTELESS‐like gene in the control of fruit set in tomato
Authors: Rojas‐Gracia Pilar , Roque Edelin , Medina Mónica , Rochina Maricruz , Hamza Rim , Angarita‐Díaz María Pilar , Moreno Vicente , Pérez‐Martín Fernando , Lozano Rafael , Cañas Luis , Beltrán José Pío , Gómez‐Mena Concepción
Published: January 2017

Fruit set is an essential process to ensure successful sexual plant reproduction. The development of the flower into a fruit is actively repressed in the absence of pollination. However, some cultivars from a few species are able to develop seedless fruits overcoming the standard restriction of unpollinated ovaries to growth.

We report here the identification of the tomato hydra mutant that produces seedless (parthenocarpic) fruits.

Seedless fruit production in hydra plants is linked to the absence of both male and female sporocyte development. The HYDRA gene is therefore essential for the initiation of sporogenesis in tomato. Using positional cloning, virus‐induced gene silencing and expression analysis experiments, we identified the HYDRA gene and demonstrated that it encodes the tomato orthologue of SPOROCYTELESS/NOZZLE (SPL/NZZ) of Arabidopsis. We found that the precocious growth of the ovary is associated with changes in the expression of genes involved in gibberellin (GA) metabolism.

Our results support the conservation of the function of SPL‐like genes in the control of sporogenesis in plants. Moreover, this study uncovers a new function for the tomato SlSPL/HYDRA gene in the control of fruit initiation.
Recent breakthroughs in metabolomics promise to reveal the cryptic chemical traits that mediate plant community composition, character evolution and lineage diversification
Authors: Sedio Brian E.
Published: January 2017

ContentsSummary952I.Introduction952II.Recent innovations in structural metabolomics953III.Species coexistence955IV.Character evolution and lineage diversification956V.Conclusions957Acknowledgements957References957

Much of our understanding of the mechanisms by which biotic interactions shape plant communities has been constrained by the methods available to study the diverse secondary chemistry that defines plant relationships with other organisms. Recent innovations in analytical chemistry and bioinformatics promise to reveal the cryptic chemical traits that mediate plant ecology and evolution by facilitating simultaneous structural comparisons of hundreds of unknown molecules to each other and to libraries of known compounds. Here, I explore the potential for mass spectrometry and nuclear magnetic resonance metabolomics to enable unprecedented tests of seminal, but largely untested hypotheses that propose a fundamental role for plant chemical defenses against herbivores and pathogens in the evolutionary origins and ecological coexistence of plant species diversity.
The Arabidopsis Elongator complex is required for nonhost resistance against the bacterial pathogens Xanthomonas citri subsp. citri and Pseudomonas syringae pv. phaseolicola NPS3121
Authors: An Chuanfu , Wang Chenggang , Mou Zhonglin
Published: January 2017

Although in recent years nonhost resistance has attracted considerable attention for its broad spectrum and durability, the genetic and mechanistic components of nonhost resistance have not been fully understood.

We used molecular and histochemical approaches including quantitative PCR, chromatin immunoprecipitation, and 3,3′‐diaminobenzidine and aniline blue staining.

The evolutionarily conserved histone acetyltransferase complex Elongator was identified as a major component of nonhost resistance against Xanthomonas citri subsp. citri (Xcc) and Pseudomonas syringae pv. phaseolicola (Psp) NPS3121. Mutations in Elongator genes inhibit Xcc‐, Psp NPS3121‐ and/or flg22‐induced defense responses including defense gene expression, callose deposition, and reactive oxygen species (ROS) and salicylic acid (SA) accumulation. Mutations in Elongator also attenuate the ROS–SA amplification loop. We show that suppressed ROS and SA accumulation in Elongator mutants is correlated with reduced expression of the Arabidopsis respiratory burst oxidase homologue AtrbohD and the SA biosynthesis gene ISOCHORISMATE SYNTHASE1 (ICS1). Furthermore, we found that the Elongator subunit ELP2 is associated with the chromatin of AtrbohD and ICS1 and is required for maintaining basal histone H3 acetylation levels in these key defense genes.

As both AtrbohD and ICS1 contribute to nonhost resistance against Xcc, our results reveal an epigenetic mechanism by which Elongator regulates nonhost resistance in Arabidopsis.
Longitudinal Study of Pediatric Urticaria Pigmentosa
Authors: Heinze Adam , Kuemmet Travis J. , Chiu Yvonne E. , Galbraith Sheila S.
Published: January 2017

Background/Objectives

Urticaria pigmentosa (UP) is the most common form of mastocytosis in children and is associated with systemic signs, symptoms, and triggers. To our knowledge, the effect of UP on children's quality of life has not been studied. The objective of the current study was to characterize the natural history, triggers, and complications of pediatric UP, identify prognostic indicators, and determine its effect on quality of life.

Methods

Between 2002 and 2007, children with three or more mastocytomas diagnosed by a pediatric dermatologist were recruited during visits at the Children's Hospital of Wisconsin Dermatology Clinic (Milwaukee, WI). Research visits were conducted every 3 years and telephone interviews yearly. The Children's Dermatology Life Quality Index was administered to subjects 4 years of age and older at enrollment. Laboratory test results were collected for subjects younger than 4 years at enrollment. Subjects were followed until UP resolution or study end in August 2015.

Results

The final cohort size was 43 subjects followed for a median of 8.1 years. Twenty‐six subjects were followed through study completion. At age 12 years, 6 patients had disease resolution and 14 remained active. Patients who had disease resolution before age 12 years were more likely to be male and had fewer years of age and smaller lesions, fewer affected areas, and earlier onset. Common medications and anesthetics resulted in no serious reactions. Hymenoptera stings occurred in 51%, with no reports of anaphylaxis. No patient reported a severe effect on quality of life, with most indicating mild to no effect.

Conclusion

Severe complications are not common with historically identified triggers. Disease does not resolve before adolescence in most children. UP has a minimal effect on quality of life for most children.
Temporal, but not spatial, changes in expression patterns of petal identity genes are associated with loss of papillate conical cells and the shift to bird pollination in Macaronesian Lotus (Leguminosae)
Authors: Ojeda D. I. , Jaén‐Molina R. , Santos‐Guerra A. , Caujape‐Castells J. , Cronk Q.
Published: January 2017

In the generally bee‐pollinated genus Lotus a group of four species have evolved bird‐pollinated flowers. The floral changes in these species include altered petal orientation, shape and texture. In Lotus these characters are associated with dorsiventral petal identity, suggesting that shifts in the expression of dorsal identity genes may be involved in the evolution of bird pollination. Of particular interest is Lotus japonicus CYCLOIDEA 2 (LjCYC2), known to determine the presence of papillate conical cells on the dorsal petal in L. japonicus. Bird‐pollinated species are unusual in not having papillate conical cells on the dorsal petal.

Using RT‐PCR at various stages of flower development, we determined the timing of expression in all petal types for the three putative petal identity genes (CYC‐like genes) in different species with contrasting floral morphology and pollination syndromes.

In bird‐pollinated species the dorsal identity gene, LjCYC2, is not expressed at the floral stage when papillate conical cells are normally differentiating in bee‐pollinated species. In contrast, in bee‐pollinated species, LjCYC2 is expressed during conical cell development.

Changes in the timing of expression of the above two genes are associated with modifications in petal growth and lateralisation of the dorsal and ventral petals in the bird‐pollinated species. This study indicates that changes in the timing, rather than spatial distribution, of expression likely contribute to the modifications of petal micromorphology and petal size during the transition from bee to bird pollination in Macaronesian Lotus species.
Quantitative approach for the early detection of selection for virulence of Meloidogyne incognita on resistant tomato in plastic greenhouses
Authors: Giné A. , Sorribas F. J.
Published: January 2017

Resistant tomato cultivars are an important tool to control Meloidogyne spp., which cause the highest yield losses attributed to plant‐parasitic nematodes. However, the repeated cultivation of Mi resistant cultivars can select virulent populations. In the present study, the susceptible tomato cv. Durinta and the resistant cv. Monika were cultivated from March to July in a plastic greenhouse for 3 years to determine the maximum multiplication rate, maximum nematode density, equilibrium density, relative susceptibility and population growth rate of M. incognita; these were used as proxy indicators of virulence and yield losses. The values of population dynamics and growth rate on the resistant tomato increased year by year and were higher when it was repeatedly cultivated in the same plot compared to when it was alternated with the susceptible cultivar and the level of resistance decreased from very to moderately resistant. The relationship between the nematode density at transplanting (Pi) and the relative yield of tomato fitted to the Seinhorst damage model for susceptible, but not resistant, cultivars. The tolerance limit and the relative minimum yield were 2–4 J2 per 250 cm3 of soil and 0.44–0.48, respectively. The tomato yield did not differ between cultivars at low Pi, but it did at higher Pi values, at which the resistant yielded 50% more than the susceptible. This study demonstrates the utility of population dynamics parameters for the early detection of selection for virulence in Meloidogyne spp., and that three consecutive years were not sufficient to select for a completely virulent population.
Evaluation of changes in oxyhemoglobin during Shiritori task in elderly subjects including those with Alzheimer‧s disease
Authors: Kato Yusuke , Shoji Yoshihisa , Morita Kiichiro , Inoue Masayuki , Ishii Yohei , Sato Mamoru , Yamashita Yuuji , Okawa Junji , Uchimura Naohisa
Published: January 2017

Background

In recent years, as the prevalence of Alzheimer‧s disease (AD) has increased rapidly, demand has increased for early detection and treatment. Therefore, discovery and treatment intervention at the mild cognitive impairment stage are important. Dysfunction of the working memory is known to be conspicuously present in AD patients or mild cognitive impairment subjects from an early stage. Near‐infrared spectroscopy (NIRS) is a method to measure hemoglobin concentration changes during an activation task. In the present study, we evaluated the cognitive function of elderly subjects, including those with AD, by means of NIRS.

Methods

The subjects were divided into three groups—the AD group, the intermediate group, and the healthy group (HG)—based on assement of dementia using the Hasegawa‧s Dementia Scale‐Revised, Mini‐Mental State Examination, and Clinical Dementia Rating. The intermediate group was divided into two groups—the high score group (HSMG) and the low score group (LSMG)—based on Hasegawa‧s Dementia Scale‐Revised and Mini‐Mental State Examination scores. In this study, during Shiritori tasks using single‐event‐related NIRS, we analyzed oxyhemoglobin changes in an area, the peak amplitude, and latency, and compared them among four groups: AD group, HSMG, LSMG, and HG.

Result

In the AD group, the area at left channel (Ch)9, 11, and 19, the area at right Ch22, and the peak ampulitude at left Ch11 and 19 and right Ch5,12, and 22 were significantly smaller than those in HSMG and HG. Furthermore, the latency of the AD group was significantly longer than that of HSMG and HG at all region of interests. However, no significant difference was observed between the AD group and LSMG.

Conclusion

These findings suggest that analysis of changes in oxyhemoglobin during Shiritori tasks may be a useful neuropsychological index for the early diagnosis of AD. Detailed studies will be conducted in LSMG to facilitate the early introduction of NIRS as a screening tool for cognitive impairment.
Frontal lobe function in elderly patients with Alzheimer's disease and caregiver burden
Authors: Hashimoto Akiko , Matsuoka Kiwamu , Yasuno Fumihiko , Takahashi Masato , Iida Junzo , Jikumaru Kiyoko , Kishimoto Toshifumi
Published: January 2017

Aim

Understanding of the relationship between caregiver burden and the degree of behavioural deficits in patients with Alzheimer's disease (AD) is relatively limited. Therefore, it is worthwhile to examine the correlations between the various relevant factors to improve the efficacy of care for patients with AD. The aim of this study was to investigate the specific contributions of frontal lobe dysfunction in AD patients to caregiver burden, while controlling for other predictor variables.

Methods

Participants included 30 pairs of caregivers and patients with AD. The Zarit Burden Interview and Frontal Assessment Battery were used to measure the caregiver burden and patients’ frontal lobe function, respectively. To investigate the effects of frontal lobe dysfunction on caregiver burden, hierarchical regression equations with steps incorporating additional predictor variables were fitted. We also performed a correlation analysis between the individual subdomains of the Zarit Burden Interview and the predictor variables.

Results

Our study suggests that the degree of frontal lobe dysfunction in AD patients predicts their caregiver burden, when other factors of daily functional limitations and neuropsychiatric symptoms are controlled. Daily functional limitations and neuropsychiatric symptoms affected caregivers’ psychosocial burden, whereas frontal lobe dysfunction affected caregivers’ burden due to the increase in the dependency of the patients.

Conclusion

Our findings indicate that to ameliorate the disabilities of patients and reduce caregiver burden, there is a need for interventions that focus on psychosocial burdens, as shown in previous studies, as well as on excessive dependency due to frontal lobe dysfunction.
Diagnostic microbiology in veterinary dermatology: present and future
Authors: Guardabassi Luca , Damborg Peter , Stamm Ivonne , Kopp Peter A. , Broens Els M. , Toutain Pierre‐Louis ,   the ESCMID Study Group for Veterinary Microbiology
Published: January 2017

Background

The microbiology laboratory can be perceived as a service provider rather than an integral part of the healthcare team.

Objectives

The aim of this review is to discuss the current challenges of providing a state‐of‐the‐art diagnostic veterinary microbiology service including the identification (ID) and antimicrobial susceptibility testing (AST) of key pathogens in veterinary dermatology.

Methods

The Study Group for Veterinary Microbiology (ESGVM) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) identified scientific, technological, educational and regulatory issues impacting the predictive value of AST and the quality of the service offered by microbiology laboratories.

Results

The advent of mass spectrometry has significantly reduced the time required for ID of key pathogens such as Staphylococcus pseudintermedius. However, the turnaround time for validated AST methods has remained unchanged for many years. Beyond scientific and technological constraints, AST methods are not harmonized and clinical breakpoints for some antimicrobial drugs are either missing or inadequate. Small laboratories, including in‐clinic laboratories, are usually not adequately equipped to run up‐to‐date clinical microbiologic diagnostic tests.

Conclusions and clinical importance

ESGVM recommends the use of laboratories employing mass spectrometry for ID and broth micro‐dilution for AST, and offering assistance by expert microbiologists on pre‐ and post‐analytical issues. Setting general standards for veterinary clinical microbiology, promoting antimicrobial stewardship, and the development of new, validated and rapid diagnostic methods, especially for AST, are among the missions of ESGVM.
COMPUTED TOMOGRAPHIC FEATURES OF INCISOR PSEUDO‐ODONTOMAS IN PRAIRIE DOGS (CYNOMYS LUDOVICIANUS)
Authors: Pelizzone Igor , Di Ianni Francesco , Volta Antonella , Gnudi Giacomo , Manfredi Sabrina , Bertocchi Mara , Parmigiani Enrico
Published: January 2017

Maxillary incisor pseudo‐odontomas are common in pet prairie dogs and can cause progressive respiratory obstruction, while mandibular pseudo‐odontomas are rarely clinically significant. The aim of this retrospective cross‐sectional study was to describe CT features of maxillary and mandibular incisor pseudo‐odontomas vs. normal incisors in a group of pet prairie dogs. All pet prairie dogs with head CT scans acquired during the period of 2013–2015 were included. A veterinary radiologist who was aware of final diagnosis reviewed CT scans and recorded qualitative features of affected and normal incisors. Mean density values for the pulp cavity and palatal and buccal dentin were also recorded. A total of 16 prairie dogs were sampled (12 normal maxillary incisors, 20 confirmed maxillary incisor pseudo‐odontomas, 20 normal mandibular incisors, 12 presumed mandibular incisor pseudo‐odontomas). Maxillary incisors with confirmed pseudo‐odontomas had a significantly hyperattenuating pulp and dentin in the reserve crown and apical zone, when compared to normal maxillary incisors. Pseudo‐odontomas appeared as enlargements of the apical zone with a globular/multilobular hyperattenuating mass formation haphazardly arranged, encroaching on midline and growing caudally and ventrally. Presumed mandibular incisor pseudo‐odontomas had similar CT characteristics. In 60% of prairie dogs with maxillary incisor pseudo‐odontomas, the hard palate was deformed and the mass bulged into the oral cavity causing loss of the palatine bone. The common nasal meatus was partially or totally obliterated in 81.8% of prairie dogs with maxillary pseudo‐odontomas. Findings supported the use of CT for characterizing extent of involvement and surgical planning in prairie dogs with pseudo‐odontomas.
Effect of ageing on hypoxic exercise cardiorespiratory, muscle and cerebral oxygenation responses in healthy humans
Authors: Puthon Lara , Bouzat Pierre , Robach Paul , Favre‐Juvin Anne , Doutreleau Stéphane , Verges Samuel
Published: January 2017

New Findings

What is the central question of this study?

This study aimed to determine the effect of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia during maximal incremental exercise.

What is the main finding and its importance?

Older healthy subjects had preserved hypoxic cardiorespiratory and tissue oxygenation responses at rest and during moderate exercise. At maximal exercise, they had a reduced hypoxic ventilatory response but similar maximal power output reduction compared with young individuals. This study suggests that until moderate exercise, hypoxic responses are preserved until the age of 70 years and therefore that ageing is not a contraindication for high‐altitude sojourn.

This study assessed the effects of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia both at rest and during incremental maximal exercise. Sixteen young (20–30 years old) and 15 older healthy subjects (60–70 years old) performed two maximal incremental cycling tests in normoxia and hypoxia (inspiratory oxygen fraction 12%). Cardiorespiratory responses, prefrontal cortex and quadriceps tissue oxygenation (near‐infrared spectroscopy) were measured during exercise as well as during hypercapnia at rest. The hypoxic ventilatory response was similar in young compared with older individuals at rest and during moderate‐intensity exercise (50% maximal power output: young 0.9 ± 0.2 versus older 1.1 ± 0.8 l min−1 %−1; P > 0.05) but larger in young subjects during high‐intensity exercise (maximal power output: 2.2 ± 0.8 versus 1.8 ± 1.1 l min−1 %−1; P < 0.05). The hypoxic cardiac response did not differ between groups both at rest and during exercise. During exercise in hypoxia, young subjects showed greater deoxygenation than older subjects, at both the prefrontal cortex and quadriceps levels. The hypoxia‐induced reduction in maximal power output (young −32 ± 5% versus older −30 ± 6%; P > 0.05) and the hypercapnic responses did not differ between groups. Older healthy and active individuals below the age of 70 years have cardiorespiratory and tissue oxygenation responses to hypoxia similar to young individuals both at rest and during moderate‐intensity exercise. Despite a lower hypoxic ventilatory response at maximal exercise, older individuals have similar oxygen desaturation and maximal power output reduction compared with young subjects.
Two-Dimensional Supersonic Thrust Vectoring Using Staggered Ramps
Authors: Montes Carlos F. , Davis Roger L.
Published: January 2017

The thrust vectoring performance of a novel nozzle mechanism was numerically investigated. The nozzle was designed for supersonic, air-breathing engines using published engine data, isentropic relationships, and piecewise quartic splines. The mechanism utilizes two staggered, adjustable ramps. A baseline inviscid numerical simulation without ramps verified the nozzle design by comparing the results to the analytical data. Nine ramp configurations were analyzed under steady-state turbulent viscous conditions, using two sets of inlet parameters corresponding to inlet conditions with and without an afterburner (AB). The realizable k – ε model was used to model the turbulence field. Area-weighted integrals of the exit flow showed superior flow deflection with the nonafterburning inlet flow parameters. Calculations of the mean flow deflection angles showed that the flow can be deflected as much as 30 deg in a given direction with the largest ramp length and angle values. The smallest ramp length (less than 5% of the nozzle length) demonstrated as much as 21 deg in flow deflection.
The tropical lapse rate steepened during the Last Glacial Maximum
Authors: Loomis Shannon E. , Russell James M. , Verschuren Dirk , Morrill Carrie , De Cort Gijs , Sinninghe Damsté Jaap S. , Olago Daniel , Eggermont Hilde , Street-Perrott F. Alayne , Kelly Meredith A.
Published: January 2017

A new temperature record from East Africa demonstrates that the tropical lapse rate steepened during the last ice age.
Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation
Authors: Lau Denise , Lan Linda Yu-Ling , Andrews Sarah F. , Henry Carole , Rojas Karla Thatcher , Neu Karlynn E. , Huang Min , Huang Yunping , DeKosky Brandon , Palm Anna-Karin E. , Ippolito Gregory C. , Georgiou George , Wilson Patrick C.
Published: January 2017

A distinct population of B cells that respond to vaccination serve as potential plasma cell precursors.