bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of combined treatment with fesoterodine and mirabegron in a pelvic congestion rat model: Results from in vitro and in vivo functional studies
Authors: Sugaya Kimio , Yamagami Hidetomi , Nishijima Saori , Kadekawa Katsumi , Hizue Masanori , Ito Yoshihiko , Yamada Shizuo
Published: November 2019

Objectives

To examine the effect of combining a nonselective muscarinic receptor antagonist, 5‐hydroxymethyl tolterodine (an active metabolite of fesoterodine), with a β3 adrenoceptor agonist, mirabegron, in a rat model of pelvic congestion.

Methods

The rat pelvic congestion model used female Sprague‐Dawley rats with their bilateral common iliac and uterine veins ligated. Expressions of M2 and M3 receptor subtypes in the urothelium and detrusor were detected by real‐time polymerase chain reaction assays. The effects of both drugs were investigated on isolated bladder strips contracted by electrical field stimulation. in vivo single cystometry was used to assess the effects of 5‐hydroxymethyl tolterodine and mirabegron independently or in combination on bladder capacity, micturition pressure, and threshold pressure.

Results

Pelvic congestion rats showed decreased bladder capacity compared with controls, but micturition pressure and threshold pressure were unchanged. Pelvic congestion model rats also demonstrated an approximately two‐fold increase in expression of both M2 and M3 receptor subtypes in the urothelium. Additive relaxant effects of 5‐hydroxymethyl tolterodine and mirabegron were observed in vitro in the electrical field stimulation‐induced contractions of bladder strips from pelvic congestion rats. In vivo, bladder capacity was increased significantly by a combination of 5‐hydroxymethyl tolterodine and mirabegron, with the combined effect exceeding the sum of the effects of monotherapies. Micturition pressure and threshold pressure did not significantly differ between groups.

Conclusions

The combination of 5‐hydroxymethyl tolterodine with mirabegron suggests the potential of synergistic effects in a rat pelvic congestion model.
Structural health monitoring using extremely compressed data through deep learning
Authors: Azimi Mohsen , Pekcan Gokhan
Published: November 2019

This study introduces a novel convolutional neural network (CNN)‐based approach for structural health monitoring (SHM) that exploits a form of measured compressed response data through transfer learning (TL)‐based techniques. The implementation of the proposed methodology allows damage identification and localization within a realistic large‐scale system. To validate the proposed method, first, a well‐known benchmark model is numerically simulated. Using acceleration response histories, as well as compressed response data in terms of discrete histograms, CNN models are trained, and the robustness of the CNN architectures is evaluated. Finally, pretrained CNNs are fine‐tuned to be adaptable for three‐parameter, extremely compressed response data, based on the response mean, standard deviation, and a scale factor. The performance of each CNN implementation is assessed using training accuracy histories as well as confusion matrices, along with other performance metrics. In addition to the numerical study, the performance of the proposed method is demonstrated using experimental vibration response data for verification and validation. The results indicate that deep TL can be implemented effectively for SHM of similar structural systems with different types of sensors.
Communicating hydrocephalus associated with neurosarcoidosis diagnosed by endoscopic biopsy
Authors: Maruno Sayako , Naito Tatsuhiko , Nakamoto Fumiko Kusunoki , Kamisawa Aya , Sato Tatsuya , Seki Tomonari , Maekawa Risa , Hideyama Takuto , Ushiku Tetsuo , Shin Masahiro , Shiio Yasushi
Published: November 2019

We present a case of communicating hydrocephalus associated with neurosarcoidosis in which the patient was diagnosed by endoscopic biopsy and successfully treated with corticosteroid therapy. The patient was a 53‐year‐old woman who presented with vertigo and nausea. Brain MRI revealed hydrocephalus and contrast‐enhancing areas only on the interthalamic adhesion. Sarcoidosis was suspected based on hilar lymphadenopathy and her past history of uveitis; however, there was no other organ involvement appropriate for biopsy. We performed endoscopic third ventriculocisternostomy and performed biopsy of nodular lesions of the interthalamic adhesion. Interestingly, endoscopy revealed numerous lesions on ventricular walls, which were not detected on contrast‐enhanced MRI. The histopathological examination revealed findings consistent with sarcoidosis. The patient was started on corticosteroid therapy, and her hydrocephalus improved conspicuously. Our case reinforces the notion that endoscopic biopsy is helpful in the definite diagnosis of neurosarcoidosis.
A juvenile case of idiopathic hypertrophic pachymeningitis involved cavernous sinus and proximal trigeminal nerve
Authors: Bian Zhihong , Omote Yoshio , Tadokoro Koh , Ikegami Ken , Osakada Yosuke , Takemoto Mami , Hishikawa Nozomi , Yamashita Toru , Ohta Yasuyuki , Abe Koji
Published: November 2019

Idiopathic hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterized by local or diffuse thickening of the cranial or spinal dura mater, which is primarily reported in adults. Here, we report a juvenile idiopathic HP case presenting diplopia and multiple cranial nerve palsies. Although cranial magnetic resonance imaging (MRI) shows evident lesions in cavernous sinus and preganglionic segment of trigeminal nerve, only cerebrospinal fluid (CSF) showed elevated protein (55 mg/dL) and myelin basic protein (MBP, 355 pg/mL) but negative systemic inflammatory markers. Steroid therapy greatly improved the symptom and the CSF data in 1 month.
Fatal granulomatous amoebic encephalitis due to free‐living amoebae in two boys in two different hospitals in Lima, Perú
Authors: Cabello‐Vílchez Alfonso Martín , Chura‐Araujo Miguel A. , Anicama Lima William E. , Vela César , Asencio Angélica Y. , García Hugo , del Carmen Garaycochea María , Náquira César , Rojas Elvis , Martínez Dalila Y.
Published: November 2019

Granulomatous amoebic encephalitis caused by free‐living amoebae is a rare condition that is difficult to diagnose and hard to treat, generally being fatal. Anti‐amoebic treatment is often delayed because clinical signs and symptoms may hide the probable causing agent misleading the appropriate diagnostic test. There are four genera of free‐living amoeba associated with human infection, Naegleria, Acanthamoeba sp., Balamuthia and Sappinia. Two boys were admitted with diagnosis of acute encephalitis. The history of having been in contact with swimming pools and rivers, supports the suspicion of an infection due to free‐living amoebae. In both cases a brain biopsy was done, the histology confirmed granulomatous amoebic encephalitis with the presence of amoebic trophozoites.
Suberin deposition in potato periderm: a novel resistance mechanism against tuber greening
Authors: Tanios Sabine , Thangavel Tamilarasan , Eyles Alieta , Tegg Robert S. , Nichols David S. , Corkrey Ross , Wilson Calum R.
Published: November 2019

Light‐induced tuber greening is one of the most important quality defects of potato. Although varietal and maturity factors are known to affect greening resistance, physiological mechanisms of resistance are poorly understood. We proposed that physiological and biochemical factors within the tuber periderm provide resistance and hypothesised that resistance is primarily related to suberin content.

We investigated differences in the tuber periderm between genotypes and tuber maturities that varied in greening propensity. We examined suberin and light‐induced pigment accumulation, and phellem cell development and studied greening propensity in mutant and chemically treated tubers with enhanced suberisation.

Resistance to greening was strongly linked to increased suberin in the periderm, which varied with variety and tuber maturity. Furthermore, greening was reduced in mutant and chemically treated tubers with enhanced suberisation. Increases in phellem cell layers and light‐induced carotenoids and anthocyanins were identified as secondary resistance factors.

Our work represents the first physiological mechanism of varietal and tuber maturity resistance to greening, expanding the known functionality of suberin and providing for the first time a biomarker that will aid producers and breeders in selection and improvement of potato varieties for greening resistance.
Disruption of Arabidopsis neutral ceramidases 1 and 2 results in specific sphingolipid imbalances triggering different phytohormone‐dependent plant cell death programmes
Authors: Zienkiewicz Agnieszka , Gömann Jasmin , König Stefanie , Herrfurth Cornelia , Liu Yi‐Tse , Meldau Dorothea , Feussner Ivo
Published: November 2019

Sphingolipids act as regulators of programmed cell death (PCD) and the plant defence response. The homeostasis between long‐chain base (LCB) and ceramide (Cer) seems to play an important role in executions of PCD. Therefore, deciphering the role of neutral ceramidases (NCER) is crucial to identify the sphingolipid compounds that trigger and execute PCD.

We performed comprehensive sphingolipid and phytohormone analyses of Arabidopsis ncer mutants, combined with gene expression profiling and microscopic analyses.

While ncer1 exhibited early leaf senescence (developmentally controlled PCD – dPCD) and an increase in hydroxyceramides, ncer2 showed spontaneous cell death (pathogen‐triggered PCD‐like – pPCD) accompanied by an increase in LCB t18:0 at 35 d, respectively. Loss of NCER1 function resulted in accumulation of jasmonoyl‐isoleucine (JA‐Ile) in the leaves, whereas disruption of NCER2 was accompanied by higher levels of salicylic acid (SA) and increased sensitivity to Fumonisin B1 (FB1). All mutants were also found to activate plant defence pathways. These data strongly suggest that NCER1 hydrolyses ceramides whereas NCER2 functions as a ceramide synthase.

Our results reveal an important role of NCER in the regulation of both dPCD and pPCD via a tight connection between the phytohormone and sphingolipid levels in these two processes.
KRAS mutations in implant‐associated peripheral giant cell granuloma
Authors: Martins‐Chaves Roberta Rayra , Guimarães Letícia Martins , Pereira Thaís dos Santos Fontes , Pereira Núbia Braga , Chrcanovic Bruno Ramos , Fonseca Felipe Paiva , Lafuente‐Ibáñez de Mendoza Irene , Aguirre‐Urizar José Manuel , Gomes Carolina Cavaliéri , Gomez Ricardo Santiago
Published: November 2019

Objectives

To investigate the molecular pathogenesis of implant‐associated peripheral giant cell granuloma (IA‐PGCG).

Methods

A convenience sample of 15 IA‐PGCG cases was selected. Hotspot mutations of KRAS, FGFR1, and TRPV4 genes, previously reported in conventional giant cell lesions of the jaws, were investigated by Sanger sequencing. As these mutations could activate MAPK/ERK pathway, the expression of phospho‐ERK1/2 was also evaluated by immunohistochemistry.

Results

KRAS mutations were detected in 8/15 (53.4%) samples. Similar to conventional peripheral giant cell granuloma, the KRAS mutations most frequently occurred in codon 146 (p.A146V, n = 3), followed by codon 12 (p.G12A and p.G12D, n = 1 each) and codon 14 (p.V14L, n = 1). Variants of unknown significance (VUS) were also detected in two cases, affecting codons 37 (p.E37K) and 127 (p.T127I). All samples showed wild‐type (WT) sequences for FGFR1 and TRPV4 genes. Consistent with MAPK/ERK pathway activation, all mononuclear cells of the lesion showed strong staining for phospho‐ERK1/2 protein in the immunohistochemical analysis.

Conclusions

KRAS mutations and activation of the MAPK‐ERK signaling pathway occur in IA‐PGCG. This is the first study to demonstrate cancer‐associated gene mutations in a non‐neoplastic reactive condition associated with dental implants.
The textually aware text
Authors: Shapiro Mary
Published: November 2019

Endnote 24 of David Foster Wallace’s Infinite Jest (1996, 985–993), entitled “JAMES O. INCANDENZA: A FILMOGRAPHY,” is a stunning example of metafictionality, recursivity, and the self‐consciousness associated with postmodern fiction. A parody of filmographies and film studies in general, ostensibly compiled after Incandenza’s death by somewhat unreliable narrators, this “fraudulent artifact” (Shields & Vollmer, 2012) is highly intertextual with both the real‐world and the main text of the novel. Rampant punning and “Easter eggs” serve not just to entertain, but to underline serious themes. Building on frequent references to Hamlet throughout the novel, the filmography is the play‐within‐the‐play, telling the tale that leads up to the death of the filmmaker, which (like that of King Hamlet) happens before the “on‐stage” action of the novel begins, but sets it in motion and informs all of it. Like the larger work it inhabits, the filmography is not (or not just) a puzzle to be solved, but a poignant narrative that contains deliberate ambiguities and has profound ethical implications.
Herbivore‐specific plant volatiles prime neighboring plants for nonspecific defense responses
Authors: Paudel Timilsena Bipana , Seidl‐Adams Irmgard , Tumlinson James H.
Published: November 2019

Plants produce species‐specific herbivore‐induced plant volatiles (HIPVs) after damage. We tested the hypothesis that herbivore‐specific HIPVs prime neighboring plants to induce defenses specific to the priming herbivore. Since Manduca sexta (specialist) and Heliothis virescens (generalist) herbivory induced unique HIPV profiles in Nicotiana benthamiana, we used these HIPVs to prime receiver plants for defense responses to simulated herbivory (mechanical wounding and herbivore regurgitant application). Jasmonic acid (JA) accumulations and emitted volatile profiles were monitored as representative defense responses since JA is the major plant hormone involved in wound and defense signaling and HIPVs have been implicated as signals in tritrophic interactions. Herbivore species‐specific HIPVs primed neighboring plants, which produced 2 to 4 times more volatiles and JA after simulated herbivory when compared to similarly treated constitutive volatile‐exposed plants. However, HIPV‐exposed plants accumulated similar amounts of volatiles and JA independent of the combination of priming or challenging herbivore. Furthermore, volatile profiles emitted by primed plants depended only on the challenging herbivore species but not on the species‐specific HIPV profile of damaged emitter plants. This suggests that feeding by either herbivore species primed neighboring plants for increased HIPV emissions specific to the subsequently attacking herbivore and is probably controlled by JA.
Comparative genome and transcriptome analysis unravels key factors of nitrogen use efficiency in Brassica napus L
Authors: Li Quan , Ding Guangda , Yang Ningmei , White Philip John , Ye Xiangsheng , Cai Hongmei , Lu Jianwei , Shi Lei , Xu Fangsen
Published: November 2019

Considerable genetic variation in agronomic nitrogen (N) use efficiency (NUE) has been reported among genotypes of Brassica napus. However, the physiological and molecular mechanisms underpinning these differences remain poorly understood. In this study, physiological and genetic factors impacting NUE were identified in field trials and hydroponic experiments using two B. napus genotypes with contrasting NUE. The results showed that the N‐efficient genotype (D4‐15) had greater N uptake and utilization efficiencies, more root tips, larger root surface and root volume, and higher N assimilation and photosynthesis capacity than the N‐inefficient genotype (D2‐1). Genomic analysis revealed that D4‐15 had a greater genome diversity related to NUE than D2‐1. By combining genomic and transcriptomic analysis, genes involved in photosynthesis and C/N metabolism were implicated in conferring NUE. Co‐expression network analysis of genes that differed between the two genotypes suggested gene clusters impacting NUE. A nitrate transporter gene BnaA06g04560D (NRT2.1) and two vacuole nitrate transporter CLC genes (BnaA02g11800D and BnaA02g28670D) were up‐regulated by N starvation in D4‐15 but not in D2‐1. The study revealed that high N uptake and utilization efficiencies, maintained photosynthesis and coordinated C/N metabolism confer high NUE in B. napus, and identified candidate genes that could facilitate breeding for enhanced NUE in B. napus.
Mid‐infrared spectroscopy is a fast screening method for selecting Arabidopsis genotypes with altered leaf cuticular wax
Authors: Liu Na , Zhao Lifang , Tang Lily , Stobbs Jarvis , Parkin Isobel , Kunst Ljerka , Karunakaran Chithra
Published: November 2019

Arabidopsis eceriferum (cer) mutants with unique alterations in their rosette leaf cuticular wax accumulation and composition established by gas chromatography have been investigated using attenuated total reflection (ATR)‐Fourier transform infrared (FTIR) spectroscopy in combination with univariate and multivariate analysis. Objectives of this study were to evaluate the utility of ATR‐FTIR for detection of chemical diversity in leaf cuticles, obtain spectral profiles of cer mutants in comparison with the wild type, and identify changes in leaf cuticles caused by drought stress. FTIR spectra revealed both genotype‐ and treatment‐dependent differences in the chemical make‐up of Arabidopsis leaf cuticles. Drought stress caused specific changes in the integrated area of the CH3 peak, asymmetrical and symmetrical CH2 peaks, ester carbonyl peak and the peak area ratio of ester CO to CH2 asymmetrical vibration. CH3 peak positively correlated with the total wax accumulation. Thus, ATR‐FTIR spectroscopy is a valuable tool that can advance our understanding of the role of cuticle chemistry in plant response to drought and allow selection of superior drought‐tolerant varieties from large genetic resources.
Decitabine limits escape from MEK inhibition in uveal melanoma
Authors: Gonçalves Jessica , Emmons Michael F. , Faião‐Flores Fernanda , Aplin Andrew E. , Harbour J. William , Licht Jonathan D. , Wink Márcia R. , Smalley Keiran S. M.
Published: November 2019

MEK inhibitors (MEKi) demonstrate anti‐proliferative activity in patients with metastatic uveal melanoma, but responses are short‐lived. In the present study, we evaluated the MEKi trametinib alone and in combination with drugs targeting epigenetic regulators, including DOT1L, EZH2, LSD1, DNA methyltransferases, and histone acetyltransferases. The DNA methyltransferase inhibitor (DNMTi) decitabine effectively enhanced the anti‐proliferative activity of trametinib in cell viability, colony formation, and 3D organoid assays. RNA‐Seq analysis showed the MEKi‐DNMTi combination primarily affected the expression of genes involved in G1 and G2/2M checkpoints, cell survival, chromosome segregation and mitotic spindle. The DNMTi‐MEKi combination did not appear to induce a DNA damage response (as measured by γH2AX foci) or senescence (as measured by β‐galactosidase staining) compared to either MEKi or DNMTi alone. Instead, the combination increased expression of the CDK inhibitor p21 and the pro‐apoptotic protein BIM. In vivo, the DNMTi‐MEKi combination was more effective at suppressing growth of MP41 uveal melanoma xenografts than either drug alone. Our studies indicate that DNMTi may enhance the activity of MEKi in uveal melanoma.
Characteristics of socially high‐risk pregnant women and children's outcomes
Authors: Sakai Sayaka , Nagamitsu Shinichiro , Koga Hidenobu , Kanda Hiroshi , Okamatsu Yuki , Yamagata Zentaro , Yamashita Yushiro
Published: November 2019

Background

The number of reports of child abuse and neglect in Japan has increased each year. A causal relationship between socially high‐risk pregnant women and child abuse is strongly suggested. This study aims to investigate the characteristics of socially high‐risk pregnant women and their children's outcomes, to help prevent child abuse.

Methods

In total, 2,342 births were retrospectively analyzed from medical records. We extracted the frequency, factors, and circumstances of socially high‐risk pregnant women, and the presence of social interventions for their children.

Results

There were 538 (23%) socially high‐risk pregnant women out of 2,342 cases investigated. Related factors (with duplication) were: economic problems (258 cases, 48%), mental disorders (139 cases, 26%), teenage pregnancies (112 cases, 21%), multiple pregnancies (90 cases, 17%), and pregnancy conflict (73 cases, 14%). Sixty‐four (12%) expectant mothers received their first health examination in late pregnancy or were not receiving pregnancy health examinations. An analysis of births showed neonatal intensive care unit hospitalization in 40% of the children born to socially high‐risk pregnant women. The hospital Child Abuse Prevention Committee intervened in 71 cases, and child consultation centers intervened in 55 cases. Twenty‐two children entered social care facilities and four children died of unknown causes.

Conclusions

Socially high‐risk pregnant women had various social and individual problems, and received multidisciplinary interventions for child rearing support. Antenatal assessment and multidisciplinary early intervention for socially high‐risk pregnant women are necessary to prevent child abuse.
Prognostic value of urinary TGF‐β1 in hemolytic uremic syndrome: A pilot study
Authors: Balestracci Alejandro , Roy Adriana Haydeé , Caletti María Gracia
Published: November 2019

Background

Transforming growth factor β1 (TGF‐β1) is the main profibrotic cytokine. Its urinary excretion reflects intrarenal production; thus, we conjectured that it is elevated during hemolytic uremic syndrome related to Shiga‐toxin‐producing Escherichia coli (STEC‐HUS). In this pilot study, we explored the ability of baseline TGF‐β1 excretion (exposure variable) to predict renal prognosis at 6 months (outcome variable). In a secondary investigation, we compared changes in cytokine levels during the study period between patients with opposite renal outcomes.

Methods

Urinary TGF‐β1 concentrations were measured prospectively in 24 children with STEC‐HUS on admission, and at 15, 30, 60, 90, and 180 days. Normal values were obtained from 20 healthy subjects.

Results

Baseline TGF‐β1 concentrations predicted renal outcomes with an area under the curve of 1 (95%CI 0.85–1; sensitivity 100%, specificity 100%) with the best cutoff level >293.7 pg/mg uCr. All patients with high TGF‐β1 levels developed persistent renal impairment, unlike none with low concentrations (4/4 vs. 20/0 respectively, P = 0.0001). The latter had higher cytokine levels (P < 0.05) at each time point without reaching normal concentrations (<45 pg/mg uCr).

Conclusions

Baseline urinary TGF‐β1 levels accurately predicted short‐term renal outcomes in STEC‐HUS children, and cytokine excretion during the first 6 months after diagnosis was higher among those with worse evolution. Larger studies are needed to validate these findings.
Brassinosteroids are involved in ethylene‐induced Pst DC3000 resistance in Nicotiana benthamiana
Authors: Xiong J. , He R. , Yang F. , Zou L. , Yi K. , Lin H. , Zhang D.
Published: November 2019

Plant immunity is regulated by a huge phytohormone regulation network. Ethylene(ET) and brassinosteroids (BRs) play critical roles in plant response to biotic stress; however, the relationship between BR and ET in plant immunity is unclear.

We used chemical treatments, genetic approaches and inoculation experiments to investigate the relationship between ET and BR in plant defense against Pst DC3000 in Nicotiana benthamiana.

Foliar applications of ET and BR enhanced plant resistance to Pst DC3000 inoculation, while treatment with brassinazole (BRZ, a specific BR biosynthesis inhibitor) eliminated the ET induced plant resistance to Pst DC3000. Silencing of DWARF 4(DWF4, a key BR biosynthetic gene), BRASSINOSTEROID INSENSITIVE 1 (BRI1, aBR receptor) and BRASSINOSTEROID-SIGNALING KINASE 1 (BSK1, downstream of BRI1) also neutralised the ET‐induced plant resistance to Pst DC3000. ET can induce callose deposition and reactive oxygen species (ROS) accumulation to resistPst DC3000, BRZ‐treated and gene‐silenced were completely eliminate this response.

Our results suggest BR is involved in ET‐induced plant resistance, the involvement of ET in plant resistance is possibly by the induction of callose deposition and ROS accumulation, in a BR‐dependent manner.
Population structure and host range of the potato late blight pathogen Phytophthora infestans in Peru spanning two decades
Authors: Lindqvist‐Kreuze H. , Gamboa S. , Izarra M. , Pérez W. , Correa M. Y. , Astete A. , Särkinen T. , Cueva M. , Gonzáles P.
Published: November 2019

The genetic diversity of the late blight pathogen Phytophthora infestans infecting cultivated potato and alternative hosts growing in the vicinity of fields in the main potato‐growing areas of the Peruvian Andes was characterized using collections from 1997–2013 as reference. The Peruvian P. infestans population, including previously collected and current isolates, consists of four clonal lineages (EC‐1, US‐1, PE‐3 and PE‐7) that belong to the A1 mating type and have been present in the country for decades. The first report of US‐1 was in isolates collected between 1982 and 1986; meanwhile, EC‐1 and PE‐3 appeared for the first time in isolates from 1992 and PE‐7 was found in 1997. The pathogen has a very broad host range among the solanaceous plants infecting cultivated potato, tomato, pear melon and several wild species. The solanaceous species growing in the vicinity of the potato fields sampled were identified and surveyed for late blight‐like symptoms. Phytophthora infestans was isolated from nine wild species, including three new host species: Solanum zahlbruckneri, Solanum grandidentatum and Iochroma grandiflorum. There was no clear host specialization, but geographical substructuring was found as well as changes in the pathogen populations at the regional level. The clonal lineage EC‐1, which is mostly resistant to metalaxyl, has complex virulence and contains a high level of subclonal variation, continues to dominate the population. Some multilocus genotypes of the EC‐1 lineage were sampled in high frequencies and were found among the previously collected and new samples.
The expression of TwDXS in the MEP pathway specifically affects the accumulation of triptolide
Authors: Zhang Yifeng , Zhao Yujun , Wang Jiadian , Hu Tianyuan , Tong Yuru , Zhou Jiawei , Gao Jie , Huang Luqi , Gao Wei
Published: November 2019

1‐Deoxy‐d‐xylulose‐5‐phosphate synthase (DXS) is the first enzyme in the plant 2‐C‐methyl‐d‐erythritol 4‐phosphate (MEP) pathway of terpenoid synthesis. TwDXS is a prominent protein in the Tripterygium wilfordii proteome, with especially high expression in the root periderm. It is significantly regulated by methyl jasmonate. Here, we studied the influence of TwDXS expression on bioactive terpenoids in T. wilfordii. Specific fragments of TwDXS (GenBank: AKP20998.1) with lengths of 2148 and 437 bp were amplified to construct the overexpression (OE) and RNA‐interference (RNAi) vectors, respectively. After transformation of suspension cells, the expression of TwDXS and genes related to the terpenoid biosynthetic pathway was measured using qRT‐PCR. TwDXS mRNA level was 153 and 43% of the control in the OE and RNAi lines. Related genes in the 2‐C‐methyl‐d‐erythritol 4‐phosphate (MEP), mevalonic acid (MVA) and downstream pathways showed similar trends to the changes of TwDXS expression. Ultra Performance Liquid Chromatography (UPLC) was employed to measure the accumulation of terpenoids. Importantly, the triptolide content showed significant differences in both the TwDXS OE (222.35% of the control) and RNAi (34.86% of the control). However, there were no obvious changes in the celastrol content. In this study, we verified that the expression of TwDXS affects triptolide but not celastrol in T. wilfordii via both TwDXS OE and RNAi experiments.
Salience, Scientific Uncertainty, and the Agenda‐Setting Power of Science
Authors: Bromley‐Trujillo Rebecca , Karch Andrew
Published: November 2019

Discussions of science and its relevance to public policy have recently taken center stage in political discourse, illustrating the values‐based nature of scientific policy decisions. This article uses an original data set of media coverage to examine the ways in which salience and media portrayals of scientific uncertainty affect the agenda‐setting process for scientific policy issues. We build upon two scholarly literatures by incorporating research on the use of science in the policy process into the study of policy diffusion among the American states. In doing so, we develop a framework for how media portrayals of scientific information can affect agenda setting. We test this framework on three scientific issues: Genetically modified food labeling, human papillomavirus vaccinations, and indoor tanning. Our results indicate that lawmakers introduce more legislation on salient issues, while higher reported levels of scientific uncertainty reduce the likelihood of bill introductions. This finding illustrates the potential impact of national media coverage as an information transmission mechanism and the necessity of treating policy characteristics as subject to change over time.
Identification of sperm‐specific proteins associated with high fertility of Punjab Red and RIR x Local cross roosters with SDS‐PAGE and Immunoblotting
Authors: Mavi Gurjot Kaur , Dubey Prem P. , Cheema Ranjna S.
Published: November 2019

The present study aimed at characterization of fertility‐associated proteins in PR and RIR x Local roosters and was conducted on two generations of birds. Roosters were divided into high‐ (>50%) and low‐fertility groups (<50%) based on sperm function tests and fertility rate in both the generations. Polyclonal antibodies were raised in rabbits against sperm proteins of first generation highly fertile roosters and tested for characterization of fertility‐associated sperm proteins in the second generation of same roosters. IgG fraction against proteins (anti‐SP IgG) was reacted with sperm proteins of both high and low fertile roosters of second generation on immunoblots. SDS‐PAGE of sperm extracts of PR and RIR x Local cross breeds resulted in resolution of 12 and 23 proteins on 12% acrylamide gels and anti‐SP IgG reacted only with 8 and 9 sperm proteins of PR and RIR x Local cross roosters on immunoblots. The SDS‐PAGE and immunoblotting analysis also indicated a variation in sperm proteins among two breeds and high/low fertile roosters. It can be concluded that the selection of roosters on the based on proteins of 65/ 25; 70/ 46/ 30 kDa may be specifically associated with high fertility of PR and RIR x Local cross, respectively. The proteins 62 kDa (PR) and 40kDa (RIR x Local cross) may be specifically responsible for low fertility.
Resettlement challenges and dilemmas: An in‐depth case study of Bhutanese refugee women in Australia
Authors: Parajuli Jamuna , Horey Dell , Avgoulas Maria‐Irini
Published: November 2019

In this paper, the perceptions of Bhutanese refugee women were explored in relation to their changing identity and their behavioural responses in the use of preventive health services following resettlement. Interviews with 30 Bhutanese refugee women in Melbourne revealed resettlement drivers, challenges and dilemmas. There was no option for women other than resettlement, women wanted to escape from bad conditions and hopes for a better future for their children was critical in their thinking. Resettlement introduced new unexpected challenges including cultural discontinuity, changed dependency and a sense of not belonging. Dilemmas were apparent in their experiences including: despondency and contentment, gratitude and regret; and identifying as either Australian or refugee. Motherhood was important to women in this study and was challenged by changed dependency with their children in resettlement. Challenges of cultural discontinuity included the impact of communication difficulties and illiteracy and the absence of social connections with neighbours. A better understanding of how changing identities of women interact should lead to more effective strategies including tailored programs and activities.
Epstein‐Barr virus infections are strongly dependent on activating and inhibitory KIR‐HLA pairs after T‐cell replate unrelated hematopoietic stem cell transplantation, the principles, and method of pairing analysis
Authors: Nowak Jacek , Gwozdowicz Sławomir , Graczyk‐Pol Elżbieta , Mika‐Witkowska Renata , Rogatko‐Koros Marta , Nestorowicz Klaudia , Szlendak Urszula , Malinowska Agnieszka , Kaczmarek Beata , Nasilowska‐Adamska Barbara , Tormanowska Magdalena , Szczurowska Natalia , Szypnicki Jeremi , Witkowska Agnieszka , Lasota Marta , Malinowska Ewelina , Halaburda Kazimierz
Published: November 2019

Viral infections are the main cause of increased morbidity and mortality among recipients in allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells fight virally infected cells provided directional activation of cytotoxicity. In this study, we analyzed the role of receptor‐ligand pairs that include inhibitory or activating killer cell immunoglobulin‐like receptors (KIRs) with their HLA class I ligands in the course of viral infections. The paper also presents an algorithm that allows performing automated inhibitory (i) KIR:HLA pairing and rechecking in the clinical setting. The obtained results indicate a significant adverse roles of reduced number of iKIR:HLA pairs (40% vs 9%; odds ratio [OR] = 6.67; P = .0057; 95% confidence interval [CI] 1.74‐25.62) and the presence of activating KIR:HLA pairs (15% vs 5%, OR = 3.58, P = .028, 95% CI 1.19‐10.73) in EBV infections post HSCT.
Impact of diagnostic methods on efficacy estimation – a proof‐of‐principle based on historical examples
Authors: Hahn Andreas , Meyer Christian G. , Frickmann Hagen
Published: November 2019

Introduction

Accurate diagnostic methods are essential for evaluating treatment efficacy in clinical trials, including vaccine trials. Although a plethora of studies assessing novel or modified treatment options is available, clinical trials evaluating the sensitivity and specificity of diagnostic methods in compliance with the demands of drug registration trials are scarce. We assessed the accuracy of diagnostic methods in two vaccine trials conducted in 1995 and 2009 to demonstrate the impact of sensitivity and specificity on efficacy estimations.

Methods

We applied the sensitivity‐ and specificity‐adjusted vaccine efficacy estimator of Lachenbruch for modelling the impact of test characteristics on the outcome of the two vaccine trials by varying diagnostic specificity.

Results

Because of non‐ideal diagnostic sensitivity and specificity, the estimation of vaccine efficacy is compromised. We demonstrate the impact of diagnostic accuracy on efficacy estimations with increasing confidence limits.

Conclusions

Because sensitivity and specificity less than one have a direct impact on efficacy estimations in clinical trials, evaluation of diagnostic methods should lead to a level of evidence comparable with the efficacy assessment of novel treatment options. Furthermore, statistical methods adjusted for sensitivity and specificity of diagnostic methods should be applied for efficacy estimations, or this lack of confidence has to be taken into account when interpreting the results of trials.
Strongyloidiasis screening in migrants living in Spain: systematic review and meta‐analysis
Authors: Salvador Fernando , Treviño Begoña , Bosch‐Nicolau Pau , Serre‐Delcor Núria , Sánchez‐Montalvá Adrián , Oliveira Inés , Sulleiro Elena , Aznar Mª Luisa , Pou Diana , Sao‐Avilés Augusto , Molina Israel
Published: November 2019

Objectives

To provide information regarding the prevalence of strongyloidiasis among migrants coming fromStrongyloides stercoralis‐endemic areas who reside in Spain.

Methods

Systematic review of the literature and meta‐analysis of studies showing prevalence ofS. stercoralisinfection among migrants from Latin America, Africa, Eastern Europe, Asia and Oceania who reside in Spain. We included articles published until 30 April 2019 without language restriction. The keywords used for the search included ‘Strongyloides stercoralis’, ‘strongyloidiasis’, ‘Spain’, ‘screening’ and ‘migrants’.

Results

Twenty‐four studies were included in the review and meta‐analysis, comprising 12 386 screened people. Eleven studies (7020 patients) evaluated the presence ofS. stercoralisinfection only through investigation of larvae in faeces, showing an overall prevalence of 1% (95%CI 1–1%). Thirteen studies (5366 patients) used a serological test, showing an overall prevalence of 14% (95%CI 11–17%). Strongyloidiasis seroprevalence was 20% (95%CI 15–24%) among migrants from sub‐Saharan Africa, 14% (95%CI 10–18%) among those from Latin America and 8% (95%CI 5–11%) among migrants from North Africa.

Conclusions

Migrants coming from strongyloidiasis‐endemic areas living in Spain had a highS. stercoralisinfection prevalence, particularly those from sub‐Saharan Africa and Latin America. This population should be screened using serology as the most sensitive test forS. stercoralisinfection. This could be easily implemented at primary care level.
How do I incorporate red cell genotyping to improve chronic transfusion therapy?
Authors: Van Buren Nancy L. , Gorlin Jed B. , Corby Susan M. , Cassidy Sandra , FritchLilla Stephanie , Nelson Stephen C. , Westhoff Connie M.
Published: November 2019

BACKGROUND

Children with transfusion dependent anemia, such as sickle cell disease (SCD) and thalassemia, are at an increased risk for developing red blood cell (RBC) alloantibodies due to their lifelong need for transfusion therapy. With the advent of genotyping, extended RBC antigen typing can be incorporated into chronic transfusion therapy programs (CTTPs) to improve patient care and provide antigen matched blood for this population of patients.

STUDY DESIGN AND METHODS

The hospital, blood center (BC), and hematology clinic caring for children requiring long‐term transfusion support developed a CTTP. Genotyping was performed at entry to determine patient RBC antigen type. Limited versus extended antigen matching of transfusions was provided based on known RBC antibodies.

RESULTS

Fifty patients with the following disorders were enrolled: 20 with SCD, 23 with thalassemia, and 7 with other disorders. At enrollment, nine (18%) had RBC alloantibodies, including six (30%) of patients with SCD and three (13%) with thalassemia. Two children developed antibodies after enrollment; one warm autoantibody following limited “CEK” matched RBCs and one patient with a hemizygous variant RHD allele developed anti‐D. Six (30%) patients with SCD had variant RHCE alleles; two had homozygous variant alleles and four had a variant present along with a wild type allele.

CONCLUSION

We demonstrate how a CTTP can be developed in a community hospital through collaboration with the blood supplier, hospital, and clinical care team. A model of incorporating RBC genotyping informs risk for alloimmunization and allows consideration of transfusion strategy for providing prophylactic antigen matched blood.
Microsporidial keratopathy in two dogs
Authors: Scurrell Emma , Manning Sue , Malho Pedro , Civello Alex , Mould John , Carrozza Rossella , Wagner Bart E.
Published: November 2019

A microsporidial keratopathy is described in two dogs. Both dogs presented with a unilateral stromal keratopathy characterized by multifocal coalescing opacities, and the diagnosis was made on histopathologic examination of keratectomy specimens. Transmission electron microscopy (TEM) on formalin‐fixed, paraffin‐embedded corneal tissue was performed in one dog, and the morphologic features were consistent with Nosema species infection. Both dogs were initially diagnosed and treated by superficial keratectomy. One dog received additional antifungal medication and underwent a penetrating keratoplasty following local recurrence two years later. No other systemic lesions attributable to the microsporidial infection were identified clinically. The clinical and diagnostic pathology findings, treatment, and follow‐up are discussed.
Surgical outcomes of six bulldogs with spinal lumbosacral meningomyelocele or meningocele
Authors: Martín Muñiz Laura , Del Magno Sara , Gandini Gualtiero , Pisoni Luciano , Menchetti Marika , Foglia Armando , Ródenas Sergio
Published: November 2019

Objective

To report the surgical treatment and outcome of six bulldogs with spina bifida (SB) and meningocele (MC) or meningomyelocele (MMC).

Study design

Case series.

Animals

Five French bulldogs and one English bulldog with MC or MMC.

Methods

Medical records of dogs with spinal MC or MMC diagnosed by MRI at two institutions between 2013 and 2016 were reviewed for surgical treatment and outcomes.

Results

Meningocele was diagnosed in two dogs, and MMC was diagnosed in four dogs. A lumbosacral dimple was noted in all dogs along with neurological deficits most commonly consisting of urinary and fecal incontinence (n = 6) and mild/moderate paraparesis (n = 3). Dorsal laminectomy was performed in all dogs to allow dissection of the meningeal sac to the vertebral column defect. In dogs with MMC, nerves were repositioned and protruded meninges were removed prior to suturing remaining meninges. Adhesions and filum terminale were resected in two dogs with suspected tethered cord syndrome. Urinary and fecal incontinence improved in two dogs and remained unchanged in four. Paraparesis improved in two dogs.

Conclusion

Surgical treatment resulted in partial improvement of the urinary and fecal incontinence (2/6 dogs) and paraparesis (2/3 dogs) or stable neurological condition (3/6 dogs), with only minor temporary complications.

Clinical significance

In the absence of published data comparing surgical and conservative treatment of puppies affected by SB and MC or MMC, early surgical treatment can be considered to prevent deterioration of neurological signs and, eventually, facilitate improvement of neurological signs.
Ionized concentrations in Ca2+ and Mg2+ buffers must be measured, not calculated
Authors: McGuigan John A. S. , Kay James W. , Elder Hugh Y.
Published: November 2019

New Findings

What is the topic of this review?

The [Ca2+]/[Mg2+] in buffers are usually calculated using one of eight programs. These all give different values, thus [Ca2+]/[Mg2+] must be measured.

What advances does it highlight?

The ligand optimization method (LOM) using electrodes is an accurate method to do this. The limitations of the method are described. The LOM has been generalized to include calibration of fluorochromes and aequorin. It is the method of choice to measure intracellular equilibrium constants. Owing to the uncertainties for the values of resting [Ca2+], ∆[Ca2+] and the pK′ values for intracellular Ca2+/Mg2+ binding used in modelling, these values must now be re‐examined critically.

Modelling intracellular regulation of Ca2+/Mg2+ is now an established part of physiology. However, the conclusions drawn from such studies depend on accurate knowledge of intracellular [Ca2+], ∆[Ca2+] and the pK′ values for the intracellular binding of Ca2+/Mg2+. Calculation of [Ca2+]/[Mg2+] in buffers is normal. The eight freely available programs all give different values for the [Ca2+]/[Mg2+] in the buffer solutions, varying by up to a factor of 4.3. As a result, concentrations must be measured. There are two methods to do this, both based on the ligand optimization method (LOM): (1) calibration solutions from 0.5 to 4 mmol l−1; and (2) calibration solutions from 0.1 µmol l−1 to 2 mmol l−1. Both methods can be used to calibrate Ca2+/Mg2+ electrodes. Only Method 2 can be used directly to calibrate fluorochromes and aequorin. Software in the statistical program R to calculate the [Ca2+]/[Mg2+] in buffers is provided for both methods. The LOM has now been generalized for use with electrodes, fluorochromes and aequorin, making it the ideal method to determine the pK′ values for intracellular binding of Ca2+/Mg2+. The [Ca2+]/[Mg2+] in buffers must be measured routinely, which is best done by calibrating electrodes with the LOM and software written in R. If [Ca2+]/[Mg2+] in buffers are calculated, the parameters used in modelling show the same degree of variability as the software programs. Uncritical acceptance of such parameters means that conclusions reached from such studies are relative, not absolute, and must now be re‐examined.
Experiments on a Large Flexure Pivot Journal Bearing: Summary of Test Results and Comparison With Predictions
Authors: Vannini Giuseppe , Cangioli Filippo , Ciulli Enrico , Nuti Matteo , Forte Paola , Kim Jongsoo , Livermore-Hardy Richard
Published: November 2019

Flexure pivot® journal bearings (FPJBs) have typically been used in small high-speed applications such as integrally geared compressors and multistage high-speed compressors, where the temperature management and the rotordynamic stability of the machine are the main targets. Nevertheless, the need for high-speed applications may also be applicable to large compressors and for this reason a large 280 mm diameter four-pad FPJB with L/D = 0.7 has been designed, built, and tested by the Authors. The test facility is a novel rig, setup at the University of Pisa, that includes a floating test bearing and a rigid rotor supported by two stiff rolling element bearings. Both static and dynamic loads are applied through hydraulic actuators, capable of 270 kN static and 40 kN overall dynamic load. The instrumentation can measure all the relevant test boundary conditions as well as the static and dynamic quantities that characterize the bearing performance. This paper presents the results from a test campaign conceived to explore not only the design conditions (7000 rpm rotational speed and 0.75 MPa unit load) but also the sensitivity to the unit load (from 0.2 MPa minimum load up to 2.2 MPa maximum load) as well as the oil flow. The results are discussed and compared with predictions from an existing numerical code.
Analyzing Collaborations Involving Nonprofit Youth Sport Organizations: A Resource-Dependency Perspective
Authors: Jones Gareth J. , Misener Katie , Svensson Per G. , Taylor Elizabeth , Hyun Moonsup
Published: November 2019

Interorganizational relationships are a well-established practice among nonprofit youth sport organizations seeking to acquire key resources and improve service efficiencies. However, less is known about how broader trends in the nonprofit sector influence their utilization. Guided by Austin’s collaborative continuum and resource dependency theory, this study analyzed how interorganizational relationships are utilized by different nonprofit youth sport organizations in one American context. The results indicate that high-resource organizations primarily utilize philanthropic and transactional forms of collaboration, whereas integrative collaboration is more likely among low-resource organizations. The discussion draws on resource dependency theory to provide theoretical insight into this association, as well as the implications for collaborative value generated through interorganizational relationships.
Organizational Capacity and Performance of Community Sport Clubs
Authors: Doherty Alison , Cuskelly Graham
Published: November 2019

Using a multidimensional framework, the authors developed the Community Sport Capacity Scale to measure the key elements of capacity in community sport organizations or clubs and investigate their relative impact on three key indicators of club performance. Presidents or their representatives from 336 community sport organizations in 20 sports across the province of Ontario, Canada, completed the web-based survey measuring the extent of various elements of human resources, infrastructure, finance, planning, and external relationships capacity. The survey also measured club operations, programs, and community presence, identified as key performance outcomes. Controlling for club size, elements representing all five capacity dimensions were significantly associated with the outcomes. The findings highlight the rich information that may be generated from a multidimensional and context-specific perspective on organizational capacity, and indicate implications for building capacity in community sport organizations.