bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyglucosan bodies in intramuscular nerve branches are a poor predictor of GBE1 mutation and adult polyglucosan body disease
Authors: Furtado Larissa V. , Kadri Sabah , Wurst Michelle N. , Long Bradley C. , Segal Jeremy P. , Pytel Peter
Published: December 2015

Introduction: Adult polyglucosan body disease (APBD) is associated with formation of polyglucosan bodies in peripheral nerve branches. Some muscle biopsies show these inclusions in intramuscular nerve branches. It has not been established whether the presence of multiple polyglucosan bodies in intramuscular peripheral nerve branches could or should suggest testing for APBD. Methods: Fifteen muscle biopsies from adults between the ages of 36 and 84 years, all showing polyglucosan bodies in intramuscular peripheral nerve twigs, were tested by sequencing of the GBE1 gene. Results: In 4 patients, testing identified heterozygous missense mutations not previously described. No homozygous or compound heterozygous mutations were identified. Conclusions: The presence of polyglucosan bodies in intramuscular nerve twigs by itself, even if they are multiple, is not an indication of APBD. Further testing may only be indicated in patients with clinical disease manifestations. Muscle Nerve 53: 473–475, 2016
Common errors in mass spectrometry‐based analysis of post‐translational modifications
Authors: Kim Min‐Sik , Zhong Jun , Pandey Akhilesh
Published: December 2015

Mass spectrometry (MS) is a powerful tool to analyze complex mixtures of proteins in a high‐throughput fashion. Proteome analysis has already become a routine task in biomedical research with the emergence of proteomics core facilities in most research institutions. Post‐translational modifications (PTMs) represent a mechanism by which complex biological processes are orchestrated dynamically at the systems level. MS is rapidly becoming popular to discover new modifications and novel sites of known PTMs, revolutionizing the current understanding of diverse signaling pathways and biological processes. However, MS‐based analysis of PTMs has its own caveats and pitfalls that can lead to erroneous conclusions. Here, we review the most common errors in MS‐based PTM analyses with the goal of adopting strategies that maximize correct interpretation in the context of biological questions that are being addressed. Finally, we provide suggestions that should help mass spectrometrists, bioinformaticians and biologists to perform and interpret MS‐based PTM analyses more accurately.
β‐Bisabolene, a Sesquiterpene from the Essential Oil Extract of Opoponax (Commiphora guidottii), Exhibits Cytotoxicity in Breast Cancer Cell Lines
Authors: Yeo Syn Kok , Ali Ahmed Y. , Hayward Olivia A. , Turnham Daniel , Jackson Troy , Bowen Ifor D. , Clarkson Richard
Published: December 2015

The essential oils from Commiphora species have for centuries been recognized to possess medicinal properties. Here, we performed gas chromatography‐mass spectrometry on the essential oil from opoponax (Commiphora guidotti) and identified bisabolene isomers as the main constituents of this essential oil. Opoponax essential oil, a chemical component; β‐bisabolene and an alcoholic analogue, α‐bisabolol, were tested for their ability to selectively kill breast cancer cells. Only β‐bisabolene, a sesquiterpene constituting 5% of the essential oil, exhibited selective cytotoxic activity for mouse cells (IC50 in normal Eph4: >200 µg/ml, MG1361: 65.49 µg/ml, 4T1: 48.99 µg/ml) and human breast cancer cells (IC50 in normal MCF‐10A: 114.3 µg/ml, MCF‐7: 66.91 µg/ml, MDA‐MB‐231: 98.39 µg/ml, SKBR3: 70.62 µg/ml and BT474: 74.3 µg/ml). This loss of viability was because of the induction of apoptosis as shown by Annexin V‐propidium iodide and caspase‐3/7 activity assay. β‐bisabolene was also effective in reducing the growth of transplanted 4T1 mammary tumours in vivo (37.5% reduction in volume by endpoint). In summary, we have identified an anti‐cancer agent from the essential oil of opoponax that exhibits specific cytotoxicity to both human and murine mammary tumour cells in vitro and in vivo, and this warrants further investigation into the use of β‐bisabolene in the treatment of breast cancers. Copyright © 2015 John Wiley & Sons, Ltd.
Chaotic map‐based time‐aware multi‐keyword search scheme with designated server
Authors: Zhou Yousheng , Xu Guangxia , Wang Yong , Wang Xiaojun
Published: December 2015

The cloud storage service has been widely used in daily life because of its convenience. However, the service frequently suffers confidentiality problems. To address this problem, some efforts have been made on keyword search over encrypted data schemes. For instance, the chaotic‐based keyword search scheme over encrypted data has been proposed recently. However, the scheme just only support single‐ keyword search each time, which severely limits its utilization in cloud storage. This article proposes a novel chaotic‐based time‐aware multi‐keyword search scheme with designated server. Inner product similarity is adopted in our scheme to realize multiple keyword search and remove the constraint of single‐keyword search each time. Timed‐release encryption is integrated into the proposed scheme at the same time, which enables the data sender to specify the time when the cloud servers can search the encrypted data. Analysis indicates that our scheme not only can counter off‐line guessing attacks to the ciphertext and trapdoor, but also supports ranked search with a reasonable computational cost. Copyright © 2015 John Wiley & Sons, Ltd.
Severity of Acute Cholecystitis and Risk of Iatrogenic Bile Duct Injury During Cholecystectomy, a Population‐Based Case–Control Study
Authors: Törnqvist Björn , Waage Anne , Zheng Zongli , Ye Weimin , Nilsson Magnus
Published: December 2015

Background

Acute cholecystitis is a common complication to gallstone disease. The relation between the severity of acute cholecystitis and risk of bile duct injury during cholecystectomy has not yet been addressed and is the main focus of this study.

Methods

All cases with iatrogenic bile duct injury during cholecystectomy, within the Lake Mälaren region, Sweden, were identified through ICD procedure codes for biliary reconstruction within the Swedish Inpatient Register and matched to non‐injured cholecystectomized controls. Information regarding perioperative variables was collected through medical record review.

Results

After review, 158 cases and 623 controls remained for analyses. Adjusted risk of bile duct injury was doubled among patients with acute cholecystitis (OR 1.97 95 % CI 1.05–3.72), whereas a mild acute cholecystitis (Tokyo grade I) did not affect the risk of bile duct injury (OR 0.96 95 % CI 0.41–2.25), a moderate (Tokyo grade II) more than doubled the risk (OR 2.41 95 % CI 1.21–4.80). Severe cholecystitis (Tokyo grade III) had a close to significant eightfold increase in risk (OR 8.43 95 % CI 0.97–72.9). The intention to use intraoperative cholangiography reduced injury risk by 52 % (OR 0.48, 95 % CI 0.29–0.81).

Conclusions

Patients with on‐going acute cholecystitis had twice the risk of sustaining a biliary lesion compared to patients without acute cholecystitis. There was a relation between the Tokyo guidelines severity grading of acute cholecystitis and injury risk and the intention to use intraoperative cholangiography halved the risk of reconstructed bile duct injury during cholecystectomy.
Where Oncologic and Surgical Complication Scoring Systems Collide: Time for a New Consensus for CRS/HIPEC
Authors: Lehmann Kuno , Eshmuminov Dilmurodjon , Slankamenac Ksenija , Kranzbühler Benedict , Clavien Pierre‐Alain , Vonlanthen René , Gertsch Philippe
Published: December 2015

Introduction

Morbidity and mortality rates after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are important quality parameters to compare peritoneal surface malignancy centers. A major problem to assess postoperative outcomes among centers is the inconsistent reporting due to two coexisting systems, the diagnose‐based common terminology criteria for adverse events (CTCAE) classification and the therapy‐oriented Clavien‐Dindo classification. We therefore assessed and compared both reporting systems.

Patients and Methods

Complications after CRS/HIPEC were recorded in 147 consecutive patients and independently graded by an expert board using both systems. In a next step, a group of residents, experienced surgeons, and medical oncologists evaluated a set of twelve real complications, either with the Clavien‐Dindo or CTCAE classification.

Results

The postoperative complication rate after CRS/HIPEC was 37 % (54/147), 6.8 % (10/147) were reoperated, and three (2 %) patients died. The most frequent complications were intestinal fistula or abscess, pulmonary complications, and ileus. Grading of complications with the CTCAE classification resulted in a significantly higher major morbidity rate compared to the Clavien‐Dindo classification (25 vs. 8 %, p = 0.001). Evaluating a set of complications, residents, surgeons, and oncologists correctly assessed significantly more complications with the Clavien‐Dindo compared to the CTCEA classification (p < 0.001). In addition, all participants evaluated the Clavien‐Dindo classification as more simple. Residents (p < 0.001) and surgeons (p < 0.01) required less time with the Clavien‐Dindo classification; there was no difference for oncologist.

Conclusion

In conclusion, our data indicate that there is a different interpretation of severity grades of complications after CRS/HIPEC between the two classifications. There is a need for a common language in the field of CRS/HIPEC, which should be defined by a new consensus to compare surgical outcomes.
Variation of morphological and chemical traits in sexes of the dioecious perennial grassPoa ligularisin relation to shrub cover and aridity in Patagonian ecosystems
Authors: Moreno Laura , Bertiller Mónica B.
Published: December 2015

Sexes of dioecious species may have dimorphic responses to environmental variation due to differences in resource requirements and reproductive costs. We analyzed the effect of aridity/relative shrub cover, and vicinity to shrub patches on morpho‐chemical traits of sexes of the dioecious perennial grassPoa ligularisin patchy arid ecosystems in northern‐central Patagonia. We hypothesized that sexes ofP. ligularishave dimorphic responses in morpho‐chemical traits in relation to the environmental variation induced by aridity/relative shrub cover and vicinity to shrub patches. We selected seven sites across a gradient of increasing aridity and relative shrub cover. We randomly collected 5–10P. ligularisplants per site registering the sex (female or male) and location with respect to shrub patches (shrub patch or inter‐patch). For each plant, we assessed morpho‐chemical traits (height of the vegetative tillers, length/dry weight/area of blades, specific blade area, nitrogen and soluble phenol concentration in blades). Sexes showed dimorphic responses in height of vegetative tillers, blade length, and blade area with respect to vicinity to shrub patches; and in variation of soluble phenolics in blades in relation to aridity/relative shrub cover. Responses in both sexes were opposite to those expected by aridity, highlighting the role of favorable environments induced by shrub canopies on dimorphic responses of sexes ofP. ligularis.Resource‐rich microsites associated with shrub canopies promoted increased plant performance of females with high reproductive costs while resource‐poor open areas, favorable for pollen dispersal, induced improved chemical defenses of males. These results are consistent with the resource availability hypothesis.
Accuracy of Dual Phase Single-Photon Emission Computed Tomography/Computed Tomography in Primary Hyperparathyroidism: Correlation with Serum Parathyroid Hormone Levels
Authors: Koberstein Wade , Fung Christopher , Romaniuk Kristy , Abele Jonathan T.
Published: December 2015

Purpose

The objectives of this study were: 1) to determine the accuracy of dual-phase 99mTc -methoxyisobutylisonitrile (MIBI) with single-photon emission computed tomography/computed tomography (SPECT/CT) for the preoperative localization of parathyroid adenomas in the setting of primary hyperparathyroidism; 2) to determine the accuracy of localization for ectopic glands; and 3) to assess the relationship between accuracy and serum parathyroid hormone (PTH) levels.

Methods

Eighty-eight patients who underwent 99mTc-MIBI SPECT/CT imaging for primary hyperparathyroidism at our institution over a 27-month period were retrospectively assessed. The preoperative SPECT/CT results were compared to intraoperative findings (within 1 year of imaging). The relationship between serum PTH level (within 3 months) and SPECT/CT accuracy was then evaluated.

Results

Accuracy indices for the retrothyroid subgroup were sensitivity 86.7%, specificity 96.4%, positive predictive value 98.1%, negative predictive value 77.1%, and accuracy 89.8%. Accuracy indices for ectopic parathyroid adenomas were sensitivity 81.5%, specificity 100%, positive predictive value 100%, negative predictive value 92.4%, and accuracy 94.3%. For the overall group, SPECT/CT demonstrated a sensitivity of 85.1% and a PPV of 98.7%. SPECT/CT correctly identified the abnormal parathyroid gland in 60% of patients with a normal serum PTH (<6.9 pmol/L), 73% between 6.9-9.9 pmol/L, 86% between 10.0-14.9 pmol/L, 100% between 15.0-19.9 pmol/L, 88% between 20.0-24.5 pmol/L, and 100% of patients with a PTH greater than 25.0 pmol/L.

Conclusions

Dual-phase 99mTc- MIBI with SPECT/CT is an accurate and reliable means to correctly localize both retrothyroid and ectopic parathyroid adenomas for the purpose of surgical planning. The accuracy of SPECT/CT increases with increasing serum PTH levels.
Radiographic and Pathologic Manifestations of Uncommon and Rare Pulmonary Lesions
Authors: Pfeifer Kyle , Mian Ali , Adebowale Adeniran , Alomari Ahmed , Kalra Vivek , Krejci Elise , Shin Myung Soo
Published: December 2015

Pulmonary opacities/nodules are common findings on computed tomography examinations, which may represent an underlying infections or malignancy. However, not every pulmonary nodule or opacity represents malignancy or infection. We present a pictorial essay illustrating common as well as obscure noninfectious, nonmalignant pulmonary lesions. Lesions discussed include organizing pneumonia, Langerhans cell histiocytosis, pulmonary amyloidosis, hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibroblastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of these rare lesions.
Outcomes of single‐ or dual‐chamber implantable cardioverter defibrillator systems in Japanese patients
Authors: Ueda Akiko , Oginosawa Yasushi , Soejima Kyoko , Abe Haruhiko , Kohno Ritsuko , Ohe Hisaharu , Momose Yuichi , Nagaoka Mika , Matsushita Noriko , Hoshida Kyoko , Miwa Yosuke , Miyakoshi Mutsumi , Togashi Ikuko , Maeda Akiko , Sato Toshiaki , Yoshino Hideaki
Published: December 2015

Background

There are no criteria for selecting single‐ or dual‐chamber implantable cardioverter defibrillators (ICDs) in patients without a pacing indication. Recent reports showed no benefit of the dual‐chamber system despite its preference in the United States. As data on ICD selection and respective outcomes in Japanese patients are scarce, we investigated trends regarding single‐ and dual‐chamber ICD usage in Japan.

Methods

Data from a total of 205 ICD recipients with structural heart disease (median age, 63 years) in two Japanese university hospitals were reviewed. Patients with bradycardia with a pacing indication and permanent atrial fibrillation at implantation were excluded.

Results

Single‐ and dual‐chamber ICDs were implanted in 36 (18%) and 169 (82%) patients, respectively. Non‐ischemic cardiomyopathy dominated both groups. Seventeen dual‐chamber patients developed atrial pacing‐dependency over 4.5 years, and it developed immediately after implantation in 14. Although preoperative testing showed no sign of bradycardia in these patients, their pacing rate was set higher than it was in patients who were pacing‐independent (61 vs. 46 paces per min, p<0.01). Two single‐chamber patients (5%) underwent atrial lead insertion.

While inappropriate shock equally occurred in both groups (7 vs. 21 patients, single‐ vs. dual‐chamber, P=0.285), device‐related infection occurred only in dual‐chamber patients (0 vs. 9 patients, P=0.155). No differences in death or heart failure hospitalization were observed between groups.

Conclusions

Dual‐chamber ICDs were four‐fold more common in Japanese patients without a pacing indication. No benefit over single‐chamber ICD was observed. Newly developed atrial pacing‐dependency seemed to be limited and could have been overestimated due to higher pacing rate settings in dual‐chamber patients.
Effects of a water hammer and cavitation on jet formation in a test tube
Authors: Kiyama Akihito , Tagawa Yoshiyuki , Ando Keita , Kameda Masaharu
Published: December 2015

We investigate the motion of a gas–liquid interface in a test tube induced by a large acceleration via impulsive force. We conduct simple experiments in which the tube partially filled with a liquid falls under gravity and hits a rigid floor. A curved gas–liquid interface inside the tube reverses and eventually forms a so-called focused jet. In our experiments, there arises either vibration of the interface or an increment in the velocity of the liquid jet, accompanied by the onset of cavitation in the liquid column. These phenomena cannot be explained by a considering pressure impulse in a classical potential flow analysis, which does not account for finite speeds of sound or phase changes. Here we model such water-hammer events as a result of the one-dimensional propagation of a pressure wave and its interaction with boundaries through acoustic impedance mismatching. The method of characteristics is applied to describe pressure-wave interactions and the subsequent cavitation. The model proposed is found to be able to capture the time-dependent characteristics of the liquid jet.
Perspective Taking and Specificity of Sensory Contact in Romantic Relationships
Authors: Miron Anca M. , Wicklund Robert A. , Diestelmann Megan , Moore Taresa , Schroeder Hannah
Published: December 2015

In two studies, we examined the effects of perspective taking aimed at one's romantic partner, and type of romantic relationship (long-distance vs. geographically close) on sensory specificity. Sensory specificity is defined as selectivity in using sensory dimensions such as visual, acoustical, or tactile, in romantic interactions. Participants were undergraduate students involved in exclusive romantic relationships. In Study 1 (N = 210), a perspective-taking orientation to the partner enhanced sensory selectivity in both types of relationships. In Study 2 (N = 120), in which perspective taking was manipulated, perspective taking caused an increase in sensory specificity for partners living in the same location, and not for those in long-distance relationships. These findings underscore the importance of studying perspective taking in the context of sensory-based romantic interactions. Implications and future directions are discussed.
On Causality in the Study of Valence and Voting Behavior: An Introduction to the Symposium
Authors: Wlezien Christopher
Published: December 2015

Evans and Chzhen (2016a) challenge Clarke et al.’s (Clarke et al. 2004; Clarke et al. 2009) “valence” model of voting behavior in British elections. Specifically, they take issue with results based on individual-level analyses relating subjective performance assessments to the (self-reported) vote measured concurrently. The argument is a basic one: there is reason to think that evaluations of performance are caused by—and not causes of—the vote. That this may be true is supported by a large and growing body of research in political science, much of which focuses on economic voting (e.g., Campbell et al. 1960; Kramer 1983; Wlezien et al. 1997; Bartels 2002; Anderson, Mendes and Tverdova 2004; Evans and Andersen 2006; Ladner and Wlezien 2007; Evans and Pickup 2010). Estimates of valence effects in Clarke et al.’s individual-level analyses thus may be correspondingly biased. It is an important issue for the study of valence and also other electoral research relying on perceptual and attitudinal predictors.
Orthogonally Additive Polynomials and Orthosymmetric Maps in Banach Algebras with Properties 𝔸 and 𝔹
Authors: Alaminos J. , Brešar M. , Špenko Š. , Villena A. R.
Published: December 2015

This paper considers Banach algebras with properties 𝔸 or 𝔹, introduced recently by Alaminos et al. The class of Banach algebras satisfying either of these two properties is quite large; in particular, it includes C*-algebras and group algebras on locally compact groups. Our first main result states that a continuous orthogonally additive n-homogeneous polynomial on a commutative Banach algebra with property 𝔸 and having a bounded approximate identity is of a standard form. The other main results describe Banach algebras A with property 𝔹 and having a bounded approximate identity that admit non-zero continuous symmetric orthosymmetric n-linear maps from An into ℂ.
Chronic Instability and the Limits of Path Dependence
Authors: Bernhard Michael
Published: December 2015

Historical institutionalism challenged older forms of comparative historical analysis by moving away from purely structural explanations of historical outcomes. Instead it posited that there were critical junctures in which actors chose between institutional alternatives, which in turn led to path dependence. I examine a phenomenon neglected both by historical institutionalism and older forms of historical analysis—chronic instability. Instead of institutional lock-in, some junctures lead to periods of instability in which a series of regimes replace each other in rapid succession. Three different causal mechanisms that routinely contribute to chronic instability—external shocks, changing configurations of actors, and disjuncture between the logic of change and mechanisms of reproduction—are explored in depth. The plausibility of the theory is illustrated by an examination of regime instability in Germany from the collapse of the Empire in 1918 through the founding of the Federal Republic in 1949.
Induction of memory cytotoxic T cells to influenza A virus and subsequent viral clearance is not modulated by PB1‐F2‐dependent inflammasome activation
Authors: Lee Patricia (Hoi Yee) , Bird Nicola , MacKenzie‐Kludas Charley , Mansell Ashley , Kedzierska Katherine , Brown Lorena , McAuley Julie
Published: December 2015

Expression of the viral virulence protein PB1‐F2 during infection has been linked to NLRP3 inflammasome complex activation in macrophages and induction of early inflammatory events enhancing immunopathology during influenza disease. We sought to determine whether PB1‐F2‐specific NLRP3 inflammasome activation influenced the magnitude and/or robustness of the CD8+ T‐cell responses specific for conserved viral antigens and subsequent virus elimination. Using murine heterosubtypic viral infection models, we showed that mice infected with virus unable to produce PB1‐F2 protein showed no deficit in the overall magnitude and functional memory responses of CD8+ T cells established during the effector phase compared with those infected with wild‐type PB1‐F2‐expressing virus and were equally capable of mounting robust recall responses. These data indicate that while expression of PB1‐F2 protein can induce inflammatory events, the capacity to generate memory CD8+ T cells specific for immunodominant viral epitopes remains uncompromised.
Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction
Authors: Jiang Changtao , Xie Cen , Lv Ying , Li Jing , Krausz Kristopher W. , Shi Jingmin , Brocker Chad N. , Desai Dhimant , Amin Shantu G. , Bisson William H. , Liu Yulan , Gavrilova Oksana , Patterson Andrew D. , Gonzalez Frank J.
Published: December 2015

The farnesoid X receptor (FXR) regulates bile acid, lipid and glucose metabolism. Here we show that treatment of mice with glycine-β-muricholic acid (Gly-MCA) inhibits FXR signalling exclusively in intestine, and improves metabolic parameters in mouse models of obesity. Gly-MCA is a selective high-affinity FXR inhibitor that can be administered orally and prevents, or reverses, high-fat diet-induced and genetic obesity, insulin resistance and hepatic steatosis in mice. The high-affinity FXR agonist GW4064 blocks Gly-MCA action in the gut, and intestine-specific Fxr-null mice are unresponsive to the beneficial effects of Gly-MCA. Mechanistically, the metabolic improvements with Gly-MCA depend on reduced biosynthesis of intestinal-derived ceramides, which directly compromise beige fat thermogenic function. Consequently, ceramide treatment reverses the action of Gly-MCA in high-fat diet-induced obese mice. We further show that FXR signalling in ileum biopsies of humans positively correlates with body mass index. These data suggest that Gly-MCA may be a candidate for the treatment of metabolic disorders.
Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts
Authors: Albrengues Jean , Bertero Thomas , Grasset Eloise , Bonan Stephanie , Maiel Majdi , Bourget Isabelle , Philippe Claude , Herraiz Serrano Cecilia , Benamar Samia , Croce Olivier , Sanz-Moreno Victoria , Meneguzzi Guerrino , Feral Chloe C. , Cristofari Gael , Gaggioli Cedric
Published: December 2015

Carcinoma-associated fibroblasts (CAF) mediate the onset of a proinvasive tumour microenvironment. The proinflammatory cytokine LIF reprograms fibroblasts into a proinvasive phenotype, which promotes extracellular matrix remodelling and collective invasion of cancer cells. Here we unveil that exposure to LIF initiates an epigenetic switch leading to the constitutive activation of JAK1/STAT3 signalling, which results in sustained proinvasive activity of CAF. Mechanistically, p300-histone acetyltransferase acetylates STAT3, which, in turn, upregulates and activates the DNMT3b DNA methyltransferase. DNMT3b methylates CpG sites of the SHP-1 phosphatase promoter, which abrogates SHP-1 expression, and results in constitutive phosphorylation of JAK1. Sustained JAK1/STAT3 signalling is maintained by DNA methyltransferase DNMT1. Consistently, in human lung and head and neck carcinomas, STAT3 acetylation and phosphorylation are inversely correlated with SHP-1 expression. Combined inhibition of DNMT activities and JAK signalling, in vitro and in vivo, results in long-term reversion of CAF-associated proinvasive activity and restoration of the wild-type fibroblast phenotype.
Basal body multipotency and axonemal remodelling are two pathways to a 9+0 flagellum
Authors: Wheeler R. J. , Gluenz E. , Gull K.
Published: December 2015

Eukaryotic cilia/flagella exhibit two characteristic ultrastructures reflecting two main functions; a 9+2 axoneme for motility and a 9+0 axoneme for sensation and signalling. Whether, and if so how, they interconvert is unclear. Here we analyse flagellum length, structure and molecular composition changes in the unicellular eukaryotic parasite Leishmania during the transformation of a life cycle stage with a 9+2 axoneme (the promastigote) to one with a 9+0 axoneme (the amastigote). We show 9+0 axonemes can be generated by two pathways: by de novo formation and by restructuring of existing 9+2 axonemes associated with decreased intraflagellar transport. Furthermore, pro-basal bodies formed under conditions conducive for 9+2 axoneme formation can form a 9+0 axoneme de novo. We conclude that pro-centrioles/pro-basal bodies are multipotent and not committed to form either a 9+2 or 9+0 axoneme. In an alternative pathway structures can also be removed from existing 9+2 axonemes to convert them to 9+0.
Osteoblast Lineage Cells Play an Essential Role in Periodontal Bone Loss Through Activation of Nuclear Factor-Kappa B
Authors: Pacios Sandra , Xiao Wenmei , Mattos Marcelo , Lim Jason , Tarapore Rohinton S. , Alsadun Sarah , Yu Bo , Wang Cun-Yu , Graves Dana T.
Published: December 2015

Bacterial pathogens stimulate periodontitis, the most common osteolytic disease in humans and the most common cause of tooth loss in adults. Previous studies identified leukocytes and their products as key factors in this process. We demonstrate for the first time that osteoblast lineage cells play a critical role in periodontal disease. Oral infection stimulated nuclear localization of NF-κB in osteoblasts and osteocytes in the periodontium of wild type but not transgenic mice that expressed a lineage specific dominant negative mutant of IKK (IKK-DN) in osteoblast lineage cells. Wild-type mice were also susceptible to bacteria induced periodontal bone loss but transgenic mice were not. The lack of bone loss in the experimental group was linked to reduced RANKL expression by osteoblast lineage cells that led to diminished osteoclast mediated bone resorption and greater coupled new bone formation. The results demonstrate that osteoblast lineage cells are key contributors to periodontal bone loss through an NF-κB mediated mechanism.
Two domain-disrupted hda6 alleles have opposite epigenetic effects on transgenes and some endogenous targets
Authors: Zhang Shoudong , Zhan Xiangqiang , Xu Xiaoming , Cui Peng , Zhu Jian-Kang , Xia Yiji , Xiong Liming
Published: December 2015

HDA6 is a RPD3-like histone deacetylase. In Arabidopsis, it mediates transgene and some endogenous target transcriptional gene silencing (TGS) via histone deacetylation and DNA methylation. Here, we characterized two hda6 mutant alleles that were recovered as second-site suppressors of the DNA demethylation mutant ros1–1. Although both alleles derepressed 35S::NPTII and RD29A::LUC in the ros1–1 background, they had distinct effects on the expression of these two transgenes. In accordance to expression profiles of two transgenes, the alleles have distinct opposite methylation profiles on two reporter gene promoters. Furthermore, both alleles could interact in vitro and in vivo with the DNA methyltransferase1 with differential interactive strength and patterns. Although these alleles accumulated different levels of repressive/active histone marks, DNA methylation but not histone modifications in the two transgene promoters was found to correlate with the level of derepression of the reporter genes between the two had6 alleles. Our study reveals that mutations in different domains of HDA6 convey different epigenetic status that in turn controls the expression of the transgenes as well as some endogenous loci.
A simple coculture system shows mutualism between anaerobic faecalibacteria and epithelial Caco-2 cells
Authors: Sadaghian Sadabad Mehdi , von Martels Julius Z. H. , Khan Muhammed Tanweer , Blokzijl Tjasso , Paglia Giuseppe , Dijkstra Gerard , Harmsen Hermie J. M. , Faber Klaas Nico
Published: December 2015

Most gut bacteria are obligate anaerobes and are important for human health. However, little mechanistic insight is available on the health benefits of specific anaerobic gut bacteria. A main obstacle in generating such knowledge is the lack of simple and robust coculturing methods for anaerobic bacteria and oxygen-requiring human cells. Here, we describe the development of a coculture system for intestinal Caco-2 cells and an anaerobic symbiont, Faecalibacterium prausnitzii, making use of 50 mL culture tubes. F. prausnitzii was grown in 40 mL YCFAG-agar with glass-adhered Caco-2 cells placed on top in 10 mL DMEM medium. Grown for 18–36 h in a humidified incubator at 37 °C and 5% CO2, coverslip-attached Caco-2 cells promoted growth and metabolism of F. prausnitzii, while F. prausnitzii suppressed inflammation and oxidative stress in Caco-2 cells. F. prausnitzii did not compromise Caco-2 cell viability. Exogenously added porcine mucin also promoted growth of F. prausnitzii, suggesting that it may be part of the mechanism of Caco-2-stimulated growth of F. prausnitzii. This ‘Human oxygen-Bacteria anaerobic‘ (HoxBan) coculturing system uniquely establishes host-microbe mutualism of a beneficial anaerobic gut microbe in vitro and principally allows the analysis of host-microbe interactions of pure and mixed cultures of bacteria and human cells.
Ba1−xSrxZn2Si2O7 - A new family of materials with negative and very high thermal expansion
Authors: Thieme Christian , Görls Helmar , Rüssel Christian
Published: December 2015

The compound BaZn2Si2O7 shows a high coefficient of thermal expansion up to a temperature of 280 °C, then a transition to a high temperature phase is observed. This high temperature phase exhibits negative thermal expansion. If Ba2+ is successively replaced by Sr2+, a new phase with a structure, similar to that of the high temperature phase of BaZn2Si2O7, forms. At the composition Ba0.8Sr0.2Zn2Si2O7, this new phase is completely stabilized. The crystal structure was determined with single crystal X-ray diffraction using the composition Ba0.6Sr0.4Zn2Si2O7, which crystallizes in the orthorhombic space group Cmcm. The negative thermal expansion is a result of motions and distortions inside the crystal lattice, especially inside the chains of ZnO4 tetrahedra. Dilatometry and high temperature X-ray powder diffraction were used to verify the negative thermal expansion. Coefficients of thermal expansion partially smaller than −10·10−6 K−1 were measured.
A Microperfusion and In-Bore Oxygenator System Designed for Magnetic Resonance Microscopy Studies on Living Tissue Explants
Authors: Flint Jeremy J. , Menon Kannan , Hansen Brian , Forder John , Blackband Stephen J.
Published: December 2015

Spectrometers now offer the field strengths necessary to visualize mammalian cells but were not designed to accommodate imaging of live tissues. As such, spectrometers pose significant challenges—the most evident of which are spatial limitations—to conducting experiments in living tissue. This limitation becomes problematic upon trying to employ commercial perfusion equipment which is bulky and—being designed almost exclusively for light microscopy or electrophysiology studies—seldom includes MR-compatibility as a design criterion. To overcome problems exclusive to ultra-high magnetic field environments with limited spatial access, we have designed microperfusion and in-bore oxygenation systems capable of interfacing with Bruker’s series of micro surface-coils. These devices are designed for supporting cellular resolution imaging in MR studies of excised, living tissue. The combined system allows for precise control of both dissolved gas and pH levels in the perfusate thus demonstrating applicability for a wide range of tissue types. Its compactness, linear architecture and MR-compatible material content are key design features intended to provide a versatile hardware interface compatible with any NMR spectrometer. Such attributes will ensure the microperfusion rig’s continued utility as it may be used with a multitude of contemporary NMR systems in addition to those which are currently in development.
Self-assembly of Carbon Vacancies in Sub-stoichiometric ZrC1−x
Authors: Zhang Yanhui , Liu Bin , Wang Jingyang
Published: December 2015

Sub-stoichiometric interstitial compounds, including binary transition metal carbides (MC1−x), maintain structural stability even if they accommodate abundant anion vacancies. This unique character endows them with variable-composition, diverse-configuration and controllable-performance through composition and structure design. Herein, the evolution of carbon vacancy (VC) configuration in sub-stoichiometric ZrC1−x is investigated by combining the cluster expansion method and first-principles calculations. We report the interesting self-assembly of VCs and the fingerprint VC configuration (VC triplet constructed by 3rd nearest neighboring vacancies) in all the low energy structures of ZrC1−x. When VC concentration is higher than the critical value of 0.5 (x > 0.5), the 2nd nearest neighboring VC configurations with strongly repulsive interaction inevitably appear and meanwhile, the system energy (or formation enthalpy) of ZrC1−x increases sharply which suggests the material may lose phase stability. The present results clarify why ZrC1−x bears a huge amount of VCs, tends towards VC ordering and retains stability up to a stoichiometry of x = 0.5.
Realizing Broadband and Invertible Linear-to-circular Polarization Converter with Ultrathin Single-layer Metasurface
Authors: Li Zhancheng , Liu Wenwei , Cheng Hua , Chen Shuqi , Tian Jianguo
Published: December 2015

The arbitrary control of the polarization states of light has attracted the interest of the scientific community because of the wide range of modern optical applications that such control can afford. However, conventional polarization control setups are bulky and very often operate only within a narrow wavelength range, thereby resisting optical system miniaturization and integration. Here, we present the basic theory, simulated demonstration and in-depth analysis of a high-performance broadband and invertible linear-to-circular (LTC) polarization converter composed of a single-layer gold nanorod array with a total thickness of ~λ/70 for the near-infrared regime. This setup can transform a circularly polarized wave into a linearly polarized one or a linearly polarized wave with a wavelength-dependent electric field polarization angle into a circularly polarized one in the transmission mode. The broadband and invertible LTC polarization conversion can be attributed to the tailoring of the light interference at the subwavelength scale via the induction of the anisotropic optical resonance mode. This ultrathin single-layer metasurface relaxes the high-precision requirements of the structure parameters in general metasurfaces while retaining the polarization conversion performance. Our findings open up intriguing possibilities towards the realization of novel integrated metasurface-based photonics devices for polarization manipulation, modulation and phase retardation.
Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children
Authors: Thiering E. , Brüske I. , Kratzsch J. , Hofbauer L. C. , Berdel D. , von Berg A. , Lehmann I. , Hoffmann B. , Bauer C. P. , Koletzko S. , Heinrich J.
Published: December 2015

Severe vitamin D deficiency is known to cause rickets, however epidemiological studies and RCTs did not reveal conclusive associations for other parameters of bone health. In our study, we aimed to investigate the association between serum levels of 25(OH) vitamin D and bone turnover markers in a population-based sample of children. 25(OH)D, calcium (Ca), osteocalcin (OC) and β-Crosslaps (β-CTx) were measured in 2798 ten-year-old children from the German birth cohorts GINIplus and LISAplus. Linear regression was used to determine the association between bone turnover markers and 25(OH)D levels. 25(OH)D, OC and β-CTx showed a clear seasonal variation. A 10 nmol/l increase in 25(OH)D was significantly associated with a 10.5 ng/l decrease (p < 0.001) in β-CTx after adjustment for design, sex, fasting status, time of blood drawn, BMI, growth rate and detectable testosterone/estradiol. For OC alone no significant association with 25(OH)D was observed, whereas the β-CTx-to-OC ratio was inversely associated with 25(OH)D (−1.7% change, p < 0.001). When stratifying the analyses by serum calcium levels, associations were stronger in children with Ca levels below the median. This study in school-aged children showed a seasonal variation of 25(OH)D and the bone turnover markers OC and β-CTx. Furthermore a negative association between 25(OH)D and the bone resorption marker β-CTx was observed.
A Large-scale Survey of CRF55_01B from Men-Who-Have-Sex-with-Men in China: implying the Evolutionary History and Public Health Impact
Authors: Han Xiaoxu , Takebe Yutaka , Zhang Weiqing , An Minghui , Zhao Bin , Hu Qinghai , Xu Junjie , Wu Hao , Wu Jianjun , Lu Lin , Chen Xi , Liang Shu , Wang Zhe , Yan Hongjing , Fu Jihua , Cai Weiping , Zhuang Minghua , Liao Christina , Shang Hong
Published: December 2015

The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China, involving the co-circulation of several different lineages of HIV-1 strains, including subtype B and CRF01_AE. This expansion has created conditions that facilitate the generation of new recombinant strains. A molecular epidemiologic survey among MSM in 11 provinces/cities around China was conducted from 2008 to 2013. Based on pol nucleotide sequences, a total of 19 strains (1.95%) belonged to the CRF55_01B were identified from 975 MSM in 7 provinces, with the prevalence range from 1.5% to 12.5%. Near full length genome (NFLG) sequences from six epidemiologically-unlinked MSM were amplified for analyzing evolutionary history, an identical genome structure composed of CRF01_AE and subtype B with four unique recombination breakpoints in the pol region were identified. Bayesian molecular clock analyses for both CRF01_AE and B segments indicated that the estimated time of the most recent common ancestors of CRF55_01B was around the year 2000. Our study found CRF55_01B has spread throughout the most provinces with high HIV-1 prevalence and highlights the importance of continual surveillance of dynamic changes in HIV-1 strains, the emergence of new recombinants and the need for implementing effective prevention measures specifically targeting the MSM population in China.
The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer
Authors: Kawano Mahiru , Mabuchi Seiji , Matsumoto Yuri , Sasano Tomoyuki , Takahashi Ryoko , Kuroda Hiromasa , Kozasa Katsumi , Hashimoto Kae , Isobe Aki , Sawada Kenjiro , Hamasaki Toshimitsu , Morii Eiichi , Kimura Tadashi
Published: December 2015

Granulocyte-colony stimulating factor (G-CSF) producing malignant tumor has been reported to occur in various organs and has been associated with poor clinical outcome. The aim of this study is to investigate the significance of tumor G-CSF expression in the chemosensitivity of uterine cervical cancer. The clinical data of recurrent or advanced cervical cancer patients who were treated with platinum-based chemotherapy were analyzed. Clinical samples, cervical cancer cell lines and a mouse model of cervical cancer were employed to examine the mechanisms responsible for the development of chemoresistance in G-CSF-producing cervical cancer, focusing on myeloid-derived suppressor cells (MDSC). As a result, the tumor G-CSF expression was significantly associated with increased MDSC frequencies and compromised survival. In vitro and in vivo experiments demonstrated that the increased MDSC induced by tumor-derived G-CSF is involved in the development of chemoresistance. The depletion of MDSC via splenectomy or the administration of anti-Gr-1 antibody sensitized G-CSF-producing cervical cancer to cisplatin. In conclusion, tumor G-CSF expression is an indicator of an extremely poor prognosis in cervical cancer patients that are treated with chemotherapy. Combining MDSC-targeting treatments with current standard chemotherapies might have therapeutic efficacy as a treatment for G-CSF-producing cervical cancer.
The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis
Authors: Au Anthony , Griffiths Lyn R. , Cheng Kian-Kai , Wee Kooi Cheah , Irene Looi , Keat Wei Loo
Published: December 2015

Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95%  CI:1.11–1.58) and co-dominant models (OR = 1.24, 95%  CI:1.02–1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95%  CI:1.01–1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke.
Heterogeneity in the spread and control of infectious disease: consequences for the elimination of canine rabies
Authors: Ferguson Elaine A. , Hampson Katie , Cleaveland Sarah , Consunji Ramona , Deray Raffy , Friar John , Haydon Daniel T. , Jimenez Joji , Pancipane Marlon , Townsend Sunny E.
Published: December 2015

Understanding the factors influencing vaccination campaign effectiveness is vital in designing efficient disease elimination programmes. We investigated the importance of spatial heterogeneity in vaccination coverage and human-mediated dog movements for the elimination of endemic canine rabies by mass dog vaccination in Region VI of the Philippines (Western Visayas). Household survey data was used to parameterise a spatially-explicit rabies transmission model with realistic dog movement and vaccination coverage scenarios, assuming a basic reproduction number for rabies drawn from the literature. This showed that heterogeneous vaccination reduces elimination prospects relative to homogeneous vaccination at the same overall level. Had the three vaccination campaigns completed in Region VI in 2010–2012 been homogeneous, they would have eliminated rabies with high probability. However, given the observed heterogeneity, three further campaigns may be required to achieve elimination with probability 0.95. We recommend that heterogeneity be reduced in future campaigns through targeted efforts in low coverage areas, even at the expense of reduced coverage in previously high coverage areas. Reported human-mediated dog movements did not reduce elimination probability, so expending limited resources on restricting dog movements is unnecessary in this endemic setting. Enhanced surveillance will be necessary post-elimination, however, given the reintroduction risk from long-distance dog movements.
Acid-sensing ion channel (ASIC) 4 predominantly localizes to an early endosome-related organelle upon heterologous expression
Authors: Schwartz Verena , Friedrich Katharina , Polleichtner Georg , Gründer Stefan
Published: December 2015

Acid-sensing ion channels (ASICs) are voltage-independent proton-gated amiloride sensitive sodium channels, belonging to the DEG/ENaC gene family. Six different ASICs have been identified (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4) that are activated by a drop in extracellular pH, either as homo- or heteromers. An exception is ASIC4, which is not activated by protons as a homomer and which does not contribute to functional heteromeric ASICs. Insensitivity of ASIC4 to protons and its comparatively low sequence identity to other ASICs (45%) raises the question whether ASIC4 may have different functions than other ASICs. In this study, we therefore investigated the subcellular localization of ASIC4 in heterologous cell lines, which revealed a surprising accumulation of the channel in early endosome-related vacuoles. Moreover, we identified an unique amino-terminal motif as important for forward-trafficking from the ER/Golgi to the early endosome-related compartment. Collectively, our results show that heterologously expressed ASIC4 predominantly resides in an intracellular endosomal compartment.