bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissection of the contributions of cyclophilin genes to development and virulence in a fungal insect pathogen
Authors: Zhou Yonghong , Keyhani Nemat O. , Zhang Yongjun , Luo Zhibing , Fan Yanhua , Li Yujie , Zhou Qiaosheng , Chen Jianjun , Pei Yan
Published: May 2016

Cyclophilins are ubiquitous proteins found in all domains of life, catalyzing peptidyl‐prolylcis‐transisomerization (PPIase activity) and functioning in diverse cellular processes. The filamentous insect pathogenic fungus,Beauveria bassiana, contains 11 cyclophilin genes whose roles were probed via individual gene knockouts, construction of over‐expression strains, and a simultaneous gene knockdown strategy using tandem SiRNA. Mutants were examined for effects on conidiation, hyphal growth, cyclosporine and stress resistance, and insect virulence.BbCypAwas found to be the most highly expressed cyclophilin during growth and purified recombinant BbCypA displayed cyclosporine sensitive PPIase activity. Except for ΔBbCypA, targeted gene knockouts or overexpression of any cyclophilin resulted in temperature sensitivity (TS). Specific cyclophilin mutants showed impaired hyphal growth and differential effects on conidiation and cyclosporine resistance. Insect bioassays revealed decreased virulence for two cyclophilins (ΔBbCypEand ΔBbCyp6) and the simultaneous gene knockdown mutant constructs (SiRNA30). TheBbSiRNA30strains were unaffected in growth, conidiation, or under osmotic or cell wall perturbing stress, but did show increased resistance to cyclosporine and a TS phenotype. These results revealed common and unique roles for cyclophilins inB. bassianaand validate a method for examining the effects of multi‐gene families via simultaneous gene knockdown.
Rice false smut fungus hijacks the rice nutrients supply by blocking and mimicking the fertilization of rice ovary
Authors: Song Jie‐Hui , Wei Wei , Lv Bo , Lin Yang , Yin Wei‐Xiao , Peng You‐Liang , Schnabel Guido , Huang Jun‐Bin , Jiang Dao‐Hong , Luo Chao‐Xi
Published: May 2016

Rice false smut disease is an increasing threat to rice production in the world. Despite of best efforts, research for the infection of the fungus has yielded equivocal and conflicting results about where and how the infection is initiated and developed. Here we show a stepwise infection pattern and sophisticated regulation during this process. Initial infection occurred on the filaments, which prevented the production of mature pollen thus blocked the pollination. In the following days, the pathogen invaded the stigmas and styles, occasionally the ovaries. Expression analysis indicated that the fungus mimicked a successful fertilization process and enabled the continuous supply of nutrients for fungus to produce false smut balls. The stepwise infection of flower organs and mimicry of ovary fertilization unveiled in this study guided the rice plant into supplying nutrients for false smut ball development and represents a new and unique biological process of host pathogen interactions.
Environmental filtering decreases with fish development for the assembly of gut microbiota
Authors: Yan Qingyun , Li Jinjin , Yu Yuhe , Wang Jianjun , He Zhili , Van Nostrand Joy D. , Kempher Megan L. , Wu Liyou , Wang Yaping , Liao Lanjie , Li Xinghao , Wu Shu , Ni Jiajia , Wang Chun , Zhou Jizhong
Published: May 2016

Gut microbiota typically occupy habitats with definable limits/borders that are comparable to oceanic islands. The gut therefore can be regarded as an ‘island’ for the assembly of microbial communities within the ‘sea’ of surrounding environments. This study aims to reveal the ecological mechanisms that govern microbiota in the fish gut ‘island’ ecosystem. Taxonomic compositions, phylogenetic diversity, and community turnover across host development were analyzed via the high‐throughput sequencing of 16S rRNA gene amplicons. The results indicate that the Shannon diversity of gut microbiota in the three examined freshwater fish species all significantly decreased with host development, and the dominant bacterial taxa also changed significantly during host development. Null model and phylogenetic‐based mean nearest taxon distance (MNTD) analyses suggest that host gut environmental filtering led to the assembly of microbial communities in the fish gut ‘island’. However, the phylogenetic clustering of local communities and deterministic processes that governed community turnover became less distinct as the fish developed. The observed mechanisms that shaped fish gut microbiota seemed to be mainly shaped by the gut environment and by some other selective changes accompanying the host development process. These findings greatly enhance our understanding of stage‐specific community assembly patterns in the fish gut ecosystem.
Rhizoxin analogs, orfamide A and chitinase production contribute to the toxicity of Pseudomonas protegens strain Pf‐5 to Drosophila melanogaster
Authors: Loper Joyce E. , Henkels Marcella D. , Rangel Lorena I. , Olcott Marika H. , Walker Francesca L. , Bond Kise L. , Kidarsa Teresa A. , Hesse Cedar N. , Sneh Baruch , Stockwell Virginia O. , Taylor Barbara J.
Published: May 2016

Pseudomonas protegens strain Pf‐5 is a soil bacterium that was first described for its capacity to suppress plant diseases and has since been shown to be lethal to certain insects. Among these is the common fruit fly Drosophila melanogaster, a well‐established model organism for studies evaluating the molecular and cellular basis of the immune response to bacterial challenge. Pf‐5 produces the insect toxin FitD, but a ΔfitD mutant of Pf‐5 retained full toxicity against D. melanogaster in a noninvasive feeding assay, indicating that FitD is not a major determinant of Pf‐5's oral toxicity against this insect. Pf‐5 also produces a broad spectrum of exoenzymes and natural products with antibiotic activity, whereas a mutant with a deletion in the global regulatory gene gacA produces none of these exoproducts and also lacks toxicity to D. melanogaster. In this study, we made use of a panel of Pf‐5 mutants having single or multiple mutations in the biosynthetic gene clusters for seven natural products and two exoenzymes that are produced by the bacterium under the control of gacA. Our results demonstrate that the production of rhizoxin analogs, orfamide A, and chitinase are required for full oral toxicity of Pf‐5 against D. melanogaster, with rhizoxins being the primary determinant.
Patients’ knowledge and fear of colorectal cancer risk in inflammatory bowel disease
Authors: Lopez Anthony , Collet‐Fenetrier Benjamin , Belle Arthur , Peyrin‐Biroulet Laurent
Published: May 2016

Objective

To investigate knowledge and fear of colorectal cancer (CRC) risk in inflammatory bowel disease (IBD) patients.

Methods

A 12‐item self‐administered questionnaire, developed after a careful literature review, was administered to all consecutive IBD patients treated with infliximab who were followed up at Nancy University Hospital (Vandoeuvre‐lès‐Nancy, France) between February and May 2012.

Results

Altogether 100 patients including 72 with Crohn's disease (CD) were included. Only 7.0% of patients spontaneously mentioned CRC risk as a main feature of IBD and 37.0% as a potential IBD complication. CRC was the most feared complication by 26 patients [ulcerative colitis (UC) 46.4% vs CD 18.1%, P < 0.01]. Two‐thirds of patients knew that IBD increases CRC risk (UC 81.9% vs CD 57.1%, P = 0.02). Their main source of information was their gastroenterologist (52.0%). On the best screening method for CRC, 86.0% of the respondents mentioned colonoscopy. Only 32.0% of patients knew that it has to be performed 10 years after diagnosis. In case of dysplasia, 51.0% of the patients would not undergo colectomy (CD 59.7% vs UC 28.6%, P < 0.01), mainly due to the fear of having ostomy bags. Only one‐quarter of UC patients were aware of the chemopreventive effect of 5‐aminosalicylates on CRC risk.

Conclusions

Two‐thirds of IBD patients are aware of the risk of CRC. UC patients have a better knowledge of this risk and are more afraid of this complication. Our results underscore the need for therapeutic education about CRC in IBD patients.
Characterizing Drought in Irrigated Agricultural Systems: The Surface Water Delivery Index (SWDI)
Authors: Hoekema David J. , Ryu Jae Hyeon
Published: May 2016

Quantifying surface water shortages in arid and semiarid agricultural regions is challenging because limited water supplies are distributed over long distances based on complex water management systems constrained by legal, economic, and social frameworks that evolve with time. In such regions, the water supply is often derived in a climate dramatically different from where the water is diverted to meet agricultural demand. The existing drought indices which rely on local climate do not portray the complexities of the economic and legal constraints on water delivery. Nor do these indices quantify the shortages that occur in drought. Therefore, this research proposes a methodological approach to define surface water shortages in irrigated agricultural systems using a newly developed index termed the Surface Water Delivery Index (SWDI). The SWDI can be used to uniformly quantify surface water deficits/shortages at the end of the irrigation season. Results from the SWDI clearly illustrate how water shortages in droughts identified by the existing indices (e.g., SPI and PDSI) vary strongly both within and between basins. Some surface water entities are much more prone to water shortages than other entities based both on their source of water supply and water right portfolios.
Prediction of excessive weight gain in insulin treated patients with type 2 diabetes
Authors: Cichosz Simon Lebech , Lundby‐Christensen Louise , Johansen Mette D. , Tarnow Lise , Almdal Thomas Peter , Hejlesen Ole K. , Group The C.I.M.T. Trial
Published: May 2016

Background

Weight gain is an ongoing challenge when initiating insulin therapy in patients with type 2 diabetes mellitus (T2DM). However, if prediction of insulin‐associated weight gain was possible on an individual level, targeted initiatives could be implemented to reduce weight gain. The aim of the present study was to identify predictors of weight gain in insulin‐treated patients with T2DM.

Methods

In all, 412 individuals with T2DM were, in addition to metformin or placebo, randomized into 18‐month treatment groups with three different insulin analog treatment regimens (biphasic, aspart, detemir). Participants with excessive weight gain were defined as the group with weight gain in the 4th quartile (>6.2 kg).We developed a pattern classification method to predict individuals prone to excessive weight gain.

Results

Over the 18‐month treatment period, median weight gain among all 412 patients was 2.4 kg (95% prediction interval [PI] –5.6, 12.4 kg), whereas median weight gain for those in the upper 4th quartile (n = 103) was 8.9 kg (95% PI 6.3, 15.2 kg). No clinical baseline data were strong predictors of excessive weight gain. However, the weight gain during the first 3 months of the trial and the subsequent dose of insulin yielded a useful predictor for weight gain at the 18‐month follow‐up. Combining these two predictors into a prediction model with other clinical available information produced a receiver operating characteristic area under the curve of 0.80.

Conclusions

We have developed a prediction model that could help identify a substantial proportion of individuals with T2DM prone to large weight gain during insulin therapy.
Characterization of the Pharmacokinetics of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 in Human Whole Blood After Alcohol Consumption in a Clinical Laboratory Study
Authors: Javors Martin A. , Hill‐Kapturczak Nathalie , Roache John D. , Karns‐Wright Tara E. , Dougherty Donald M.
Published: May 2016

Background

The purpose of this study was to characterize the pharmacokinetics of 2 homologues of phosphatidylethanol (PEth) and their combined total in uncoagulated, whole blood samples taken from participants in a human clinical laboratory study after consumption of low doses of ethanol (EtOH).

Methods

As part of a larger study, 14 male and 13 female participants received either 0.25 or 0.50 g/kg oral doses of EtOH during a 15‐minute period. Blood samples were collected before and throughout 6 hours after each EtOH dose on the day of consumption and then every 3 days during the next 14 days. PEth 16:0/18:1 and PEth 16:0/18:2 levels were quantified in blood samples by HPLC/MS/MS and reported separately or as their combined total (combined PEth). Breath alcohol concentrations (BrACs) were measured concurrently with each blood collection. Transdermal alcohol concentrations were measured every 30 minutes during the entire 22‐day study to confirm the absence of drinking during a 7‐day period before and the 14‐day period after EtOH consumption.

Results

(i) Single doses of 0.25 and 0.50 g EtOH/kg produced proportional increases in BrAC and combined PEth levels of all participants; (ii) the areas under the curve (AUCs) for each participant's BrAC levels during the 6‐hour period after EtOH administration were correlated with AUCs of cPEth (calculated as the AUC of the increase above baseline for combined PEth); (iii) the mean half‐life of combined PEth, determined during the 14‐day period after EtOH consumption, was 4.6 ± 3.5 (SD) days (range: 1.0 to 13.1 days).

Conclusions

Combined PEth is a sensitive biomarker for the identification of relatively low levels of EtOH consumption. The measurement of these 2 homologues may provide additional sensitivity to identify low levels of drinking.
A Mechanistic Review of Cell Death in Alcohol‐Induced Liver Injury
Authors: Wang Shaogui , Pacher Pal , De Lisle Robert C. , Huang Heqing , Ding Wen‐Xing
Published: May 2016

Alcoholic liver disease (ALD) is a major health problem in the United States and worldwide without successful treatments. Chronic alcohol consumption can lead to ALD, which is characterized by steatosis, inflammation, fibrosis, cirrhosis, and even liver cancer. Recent studies suggest that alcohol induces both cell death and adaptive cell survival pathways in the liver, and the balance of cell death and cell survival ultimately decides the pathogenesis of ALD. This review summarizes the recent progress on the role and mechanisms of apoptosis, necroptosis, and autophagy in the pathogenesis of ALD. Understanding the complex regulation of apoptosis, necrosis, and autophagy may help to develop novel therapeutic strategies by targeting all 3 pathways simultaneously.
Alcohol Increases Delay and Probability Discounting of Condom‐Protected Sex: A Novel Vector for Alcohol‐Related HIV Transmission
Authors: Johnson Patrick S. , Sweeney Mary M. , Herrmann Evan S. , Johnson Matthew W.
Published: May 2016

Background

Alcohol use, especially at binge levels, is associated with sexual HIV risk behavior, but the mechanisms through which alcohol increases sexual risk taking are not well‐examined. Delay discounting, that is, devaluation of future consequences as a function of delay to their occurrence, has been implicated in a variety of problem behaviors, including risky sexual behavior. Probability discounting is studied with a similar framework as delay discounting, but is a distinct process in which a consequence is devalued because it is uncertain or probabilistic.

Methods

Twenty‐three, nondependent alcohol users (13 male, 10 female; mean age = 25.3 years old) orally consumed alcohol (1 g/kg) or placebo in 2 separate experimental sessions. During sessions, participants completed tasks examining delay and probability discounting of hypothetical condom‐protected sex (Sexual Delay Discounting Task, Sexual Probability Discounting Task) and of hypothetical and real money.

Results

Alcohol decreased the likelihood that participants would wait to have condom‐protected sex versus having immediate, unprotected sex. Alcohol also decreased the likelihood that participants would use an immediately available condom given a specified level of sexually transmitted infection (STI) risk. Alcohol did not affect delay discounting of money, but it did increase participants' preferences for larger, probabilistic monetary rewards over smaller, certain rewards.

Conclusions

Acute, binge‐level alcohol intoxication may increase sexual HIV risk by decreasing willingness to delay sex in order to acquire a condom in situations where one is not immediately available, and by decreasing sensitivity to perceived risk of STI contraction. These findings suggest that delay and probability discounting are critical, but heretofore unrecognized, processes that may mediate the relations between alcohol use and HIV risk.
Quantification of visual function assessment using remote eye tracking in children: validity and applicability
Authors: Kooiker Marlou J. G. , Pel Johan J. M. , Verbunt Hélène J. M. , de Wit Gerard C. , van Genderen Maria M. , van der Steen Johannes
Published: May 2016

Purpose

Measurements of visual and oculomotor functions are essential for providing tailored support to visually impaired children. In young or intellectually disabled children these measurements can be difficult or even impossible to perform. Recordings of orienting gaze in response to specific visual information, made with eye tracking, may offer a solution. The aim of this study was to observe and quantify eye tracking (ET)‐based gaze responses to provide information about visual and oculomotor functioning, and to compare this information with standard visual function assessments (VFA).

Methods

One hundred and twenty‐six visually impaired children from 1–14 years underwent a VFA. Next they underwent a remote ET test. Four aspects of oculomotor control (nystagmus, fixation, saccades, pursuit) and three visual functions (visual field, contrast, colour) were selected to compare both methods. Performance was assessed (1) during VFA using standard behavioural observation and test scores and (2) after ET by observing and scoring the eye movement recordings. Validity, in terms of agreement between results, was measured by correlation analyses. From the orienting gaze responses, quantitative parameters (gain, fixation duration and directional saccades) were calculated to characterize visual performance.

Results

Good agreement between the two test methods was found for observational assessment of oculomotor control and visual functions (correlations ranging from rs = 0.39 to rs = 0.69). The quantitative parameters of visual performance showed distinct results between children with and without specific functional impairments, both in children aged 1–6 and 7–14 years.

Conclusion

Eye tracking‐based gaze recordings are a promising tool to assess oculomotor and visual performance in a communication‐free manner. Calculating quantitative parameters from specific gaze responses could assist in the characterization of functional visual performance in children, independent of age. Gaze responses are a useful addition to standard VFA in clinical practice.
Glaucoma diagnostic capacity of optic nerve head haemoglobin measures compared with spectral domain OCT and HRT III confocal tomography
Authors: Mendez‐Hernandez Carmen , Rodriguez‐Uña Ignacio , Gonzalez‐de‐la Rosa Manuel , Arribas‐Pardo Paula , Garcia‐Feijoo Julian
Published: May 2016

Purpose

The computer program laguna onhe determines optic nerve head haemoglobin (ONH Hb) on retinal photographs based on detecting colour differences. This study compares the diagnostic capacity of Laguna ONhE with that of spectral domain optical coherence tomography (OCT) and confocal tomography (HRT III).

Methods

In a prospective, observational, cross‐sectional study, glaucomatous (n = 66) and healthy (n = 52) eyes were examined by Spectralis OCT, HRT III and Laguna ONhE. The following Laguna ONhE variables were determined: ONH Hb across the vertical disc diameter (8&20 Hb), estimated cup–disc ratio (C/D) and the glaucoma discriminant function (GDF), which combines the slope of Hb amount with the mean in 8&20 Hb. The three diagnostic methods were compared by calculating areas under ROC curves (AUCs). Correlations between variables were assessed through Spearman's rho coefficient.

Results

Areas under ROC curves (AUCs) were 0.785 (95% CI: 0.700–0.863) for GDF, 0.807 (95% CI: 0.730–0.883) for OCT retinal nerve fibre layer thickness (OCT‐RNFL) and 0.714 (95% CI: 0.618–0.810) and 0.721 (95% CI: 0.628–0.815) for the HRT III variable GPS (glaucoma probability score) and vertical C/D ratio, respectively.

Glaucoma discriminant function (GDF) was correlated with OCT‐RNFL (0.587, p 0.001; 0.507, p 0.045; and −0.119, p 0.713 for mild, moderate and advanced glaucoma, respectively), mostly so with inferior OCT‐RNFL (0.622; p < 0.001). Glaucoma discriminant function (GDF)‐HRT III correlations were lower (rim area 0.471, p < 0.0001; rim/disc area 0.426, p < 0.0001; vertical C/D −0.413, p < 0.0001; GPS −0.408, p < 0.0001; rim volume 0.341, p < 0.0001).

Conclusion

Similar diagnostic power was observed for Laguna ONhE, Spectralis OCT and HRT III.
Extracellular nicotinamide phosphoribosyltransferase, a new cancer metabokine
Authors: Grolla Ambra A , Travelli Cristina , Genazzani Armando A , Sethi Jaswinder K
Published: May 2016

In this review, we focus on the secreted form of nicotinamide phosphoribosyltransferase (NAMPT); extracellular NAMPT (eNAMPT), also known as pre‐B cell colony‐enhancing factor or visfatin. Although intracellular NAMPT is a key enzyme in controlling NAD metabolism, eNAMPT has been reported to function as a cytokine, with many roles in physiology and pathology. Circulating eNAMPT has been associated with several metabolic and inflammatory disorders, including cancer. Because cytokines produced in the tumour micro‐environment play an important role in cancer pathogenesis, in part by reprogramming cellular metabolism, future improvements in cancer immunotherapy will require a better understanding of the crosstalk between cytokine action and tumour biology. In this review, the knowledge of eNAMPT in cancer will be discussed, focusing on its immunometabolic function as a metabokine, its secretion, its mechanism of action and possible roles in the cancer micro‐environment.
Effect of glatiramer acetate on short‐term memory impairment induced by lipopolysaccharide in male mice
Authors: Mohammadi Fatemeh , Rahimian Reza , Fakhraei Nahid , Rezayat Seyed Mahdi , Javadi‐Paydar Mehrak , Dehpour Ahmad R. , Afshari Khashayar , Ejtemaei Mehr Shahram
Published: May 2016

Glatiramer acetate (GA) demonstrates neuroprotective, neurogenesis, and anti‐inflammatory properties. This study examines the probable protective effect of acute GA on lipopolysaccharide (LPS)‐induced memory impairment in male mice and further explores which routes of administration [subcutaneous (s.c.) or intracerebroventricular (i.c.v.)] exert optimum effect. Memory performance was evaluated in two‐trial recognition Y‐maze and passive‐avoidance tasks evaluating special recognition memory and fear memory, respectively. Memory impairment was induced by LPS [100 μg/kg, intraperitoneally (i.p.)], 4 h before training. In Y‐maze, GA (10, 2.5, 0.625, 0.153, and 0.03 mg/kg, s.c.; 250 μg/mouse; i.c.v.) was administered 10 min following LPS, and special memory was assayed in Y‐maze apparatus. In passive avoidance, LPS (100, 250 μg/kg; i.p.) was injected 4 h before receiving foot shock, and GA (10, 2.5; s.c.) or (250 μg/mouse; i.c.v.) was administered 4 h before the shock. Following 24 h, the fear memory was evaluated. Memory impaired significantly following LPS (100, 250 μg/kg; i.p.) in Y‐maze and passive‐avoidance tasks, P < 0.001 and P < 0.05, respectively. The data revealed that GA (250 μg/mouse, i.c.v.) and GA (10, 2.5 mg/kg; s.c.) in Y‐maze reversed memory impairment (LPS 100 μg/kg, i.p.) (P < 0.01). In passive‐avoidance task, GA (2.5, 10 mg/kg; s.c.) reversed LPS‐induced impairment and the mice showed significantly longer latency times during the retention trial (P < 0.01). GA improved memory impairment both centrally and systemically. It improved spatial recognition memory increasing the average time in the novel arm and improved fear memory increasing latency time. GA administration improved memory impairment profoundly through both systemic and central routs.
A cis‐prenyltransferase from Methanosarcina acetivorans catalyzes both head‐to‐tail and nonhead‐to‐tail prenyl condensation
Authors: Ogawa Takuya , Emi Koh‐ichi , Koga Kazushi , Yoshimura Tohru , Hemmi Hisashi
Published: May 2016

Cis‐prenyltransferase usually consecutively catalyzes the head‐to‐tail condensation reactions of isopentenyl diphosphate to allylic prenyl diphosphate in the production of (E,Z‐mixed) polyprenyl diphosphate, which is the precursor of glycosyl carrier lipids. Some recently discovered homologs of the enzyme, however, catalyze the nonhead‐to‐tail condensation reactions between allylic prenyl diphosphates. In this study, we characterize a cis‐prenyltransferase homolog from a methanogenic archaeon, Methanosarcina acetivorans, to obtain information on the biosynthesis of the glycosyl carrier lipids within it. This enzyme catalyzes both head‐to‐tail and nonhead‐to‐tail condensation reactions. The kinetic analysis shows that the main reaction of the enzyme is consecutive head‐to‐tail prenyl condensation reactions yielding polyprenyl diphosphates, while the chain lengths of the major products seem shorter than expected for the precursor of glycosyl carrier lipids. On the other hand, a subsidiary reaction of the enzyme, i.e., nonhead‐to‐tail condensation between dimethylallyl diphosphate and farnesyl diphosphate, gives a novel diterpenoid compound, geranyllavandulyl diphosphate.
Tailoring the Structure of Bioactive Glasses: From the Nanoscale to Macroporous Scaffolds
Authors: Vallet‐Regí María , Salinas Antonio J. , Arcos Daniel
Published: May 2016

Bioactive glasses have played a very important role in the development of new materials for bone tissue regeneration. The development of new synthesis and manufacturing methods allows the preparation of bioactive glasses with new chemical compositions, nanoscaled features, customized morphologies, and pore architectures. The composition of glasses can be designed at the atomic–molecular level to ensure bioactivity and beneficial effects including capabilities for enhancing osteogenesis and vascularization or to exert bactericide action. Moreover, the glasses can be prepared as mesoporous bioactive glasses, exhibiting ordered arrangements of nanometric pores. Through the control of the microstructure, glasses can be prepared to achieve suitable interactions with living cells. Finally, the scaffolds obtained with bioactive glasses must display interconnected pores over 100 μm to make possible bone cell ingrowths and angiogenesis. In this article, the advances in the field of bioactive glasses through the control of the chemical, nanometer scale, microstructural properties, and architectural features are presented and discussed. A detailed control of these four levels of matter organization will allow optimizing the biological response of bioactive glasses when used in bone tissue regeneration.
Factors associated with insulin‐induced weight gain in an Australian type 2 diabetes outpatient clinic
Authors: Yadgar‐Yalda R. , Colman P. G. , Fourlanos S. , Wentworth J. M.
Published: May 2016

Background

Insulin‐induced weight gain is a key concern for people with type 2 diabetes (T2D) and their treatment team. This study aimed to document the prevalence of insulin‐induced weight gain and its impact on cardiovascular risk factors in patients attending the Royal Melbourne Hospital diabetes clinic.

Methods

Clinical and biochemical data were extracted from a prospective clinic database and from the hospital record. These variables were correlated with the percentage weight change 1 year after starting insulin and compared between groups with or without clinically significant weight gain, defined as more than 7% of the baseline bodyweight.

Results

The population comprised 340 patients (184 male), representing 36% of people with T2D who commenced insulin at our clinic. Their mean ± SD age and duration of diabetes was 63 ± 11 and 13 ± 8 years respectively. The mean (95% CI) change in bodyweight at 1 year was 3.0 (2.5–3.5) kg, but this was not associated with deleterious changes in blood pressure or lipid profile. Weight gain was associated with higher insulin doses, the use of short‐acting insulin and with lower baseline bodyweight. Clinically significant weight gain occurred in 87 patients and was associated with glucose‐lowering regimens that included short‐acting insulin or a thiazolidinedione, whereas regimens that incorporated other oral agents, particularly sulfonylureas, were associated with less weight gain.

Conclusion

In this Australian tertiary hospital population with T2D, insulin‐induced weight gain was common but was not associated with deleterious changes in blood pressure or lipids. Treatment regimens that avoid short‐acting insulin but include oral agents other than thiazolidinediones might prevent insulin‐induced weight gain in T2D.
Management of diabetes in Indigenous communities: lessons from the Australian Aboriginal population
Authors: Nguyen H. D. , Chitturi S. , Maple‐Brown L. J.
Published: May 2016

Type 2 diabetes mellitus and other chronic cardio‐metabolic conditions are significant contributors to the large disparities in life expectancy between Indigenous and non‐Indigenous Australians. Type 2 diabetes is more prevalent from a young age among Indigenous Australians and is often preceded by a cluster of risk factors, including central obesity, dyslipidaemia, albuminuria and socio‐economic disadvantage. Management of type 2 diabetes in Australian Indigenous peoples can be challenging in the setting of limited resources and socio‐economic disadvantage. Key strategies to address these challenges include working in partnership with patients, communities and primary healthcare services (PHC, Aboriginal community controlled and government services) and working in a multidisciplinary team. Population prevention measures are required within and beyond the health system, commencing as early as possible in the life course.
Phenotypic plasticity in oysters (Crassostrea virginica) mediated by chemical signals from predators and injured prey
Authors: Scherer Avery E. , Lunt Jessica , Draper Alex M. , Smee Delbert L.
Published: May 2016

Prey organisms reduce predation risk by altering their behavior, morphology, or life history. Avoiding or deterring predators often incurs costs, such as reductions in growth or fecundity. Prey minimize costs by limiting predator avoidance or deterrence to situations that pose significant risk of injury or death, requiring them to gather information regarding the relative threat potential predators pose. Chemical cues are often used for risk evaluation, and we investigated morphological responses of oysters (Crassostrea virginica) to chemical cues from injured conspecifics, from heterospecifics, and from predatory blue crabs (Callinectes sapidus) reared on different diets. Previous studies found newly settled oysters reacted to crab predators by growing heavier, stronger shells, but that adult oysters did not. We exposed oysters at two size classes (newly settled oyster spat and juveniles ~2.0 cm) to predation risk cue treatments including predator or injured prey exudates and to seawater controls. Since both of the size classes tested can be eaten by blue crabs, we hypothesized that both would react to crab exudates by producing heavier, stronger shells. Oyster spat grew heavier shells that required significantly more force to break, an effective measure against predatory crabs, when exposed to chemical exudates from blue crabs as compared to controls. When exposed to chemical cues from injured conspecifics or from injured clams (Mercenaria mercenaria), a sympatric bivalve, shell mass and force were intermediate between predator treatments and controls, indicating that oysters react to injured prey cues but not as strongly as to cues released by predators. Juvenile oysters of ~ 2.0 cm did not significantly alter their shell morphology in any of the treatments. Thus, newly settled oysters can differentiate between predatory threats and adjust their responses accordingly, with the strongest responses being to exudates released by predators, but oysters of 2.0 cm and larger do not react morphologically to predatory threats.
MDA‐5 activation by cytoplasmic double‐stranded RNA impairs endothelial function and aggravates atherosclerosis
Authors: Asdonk Tobias , Steinmetz Martin , Krogmann Alexander , Ströcker Christine , Lahrmann Catharina , Motz Inga , Paul‐Krahe Kathrin , Flender Anna , Schmitz Theresa , Barchet Winfried , Hartmann Gunther , Nickenig Georg , Zimmer Sebastian
Published: May 2016

Recent studies have highlighted the relevance of viral nucleic acid immunorecognition by pattern recognition receptors in atherogenesis. Melanoma differentiation associated gene 5 (MDA‐5) belongs to the intracellular retinoic acid inducible gene‐I like receptors and its activation promotes pro‐inflammatory mechanisms. Here, we studied the effect of MDA‐5 stimulation in vascular biology. To gain insights into MDA‐5 dependent effects on endothelial function, cultured human coronary artery endothelial cells (HCAEC) were transfected with the synthetic MDA‐5 agonist polyIC (long double‐stranded RNA). Human coronary endothelial cell expressed MDA‐5 and reacted with receptor up‐regulation upon stimulation. Reactive oxygen species formation, apoptosis and the release of pro‐inflammatory cytokines was enhanced, whereas migration was significantly reduced in response to MDA‐5 stimulation. To test these effects in vivo, wild‐type mice were transfected with 32.5 μg polyIC/JetPEI or polyA/JetPEI as control every other day for 7 days. In polyIC‐treated wild‐type mice, endothelium‐dependent vasodilation and re‐endothelialization was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticles and circulating endothelial progenitor cells significantly elevated compared to controls. Importantly, these effects could be abrogated by MDA‐5 deficiency in vivo. Finally, chronic MDA‐5 stimulation in Apolipoprotein E/toll‐like receptor 3 (TLR3) double‐deficient (ApoE−/−/TLR3−/−) mice‐enhanced atherosclerotic plaque formation. This study demonstrates that MDA‐5 stimulation leads to endothelial dysfunction, and has the potential to aggravate atherosclerotic plaque burden in murine atherosclerosis. Thus, the spectrum of relevant innate immune receptors in vascular diseases and atherogenesis might not be restricted to TLRs but also encompasses the group of RLRs including MDA‐5.
Sleep disturbance and enhanced esophageal capsaicin sensitivity in patients with gastroesophageal reflux disease
Authors: Yi Chih‐Hsun , Lei Wei‐Yi , Hung Jui‐Sheng , Liu Tso‐Tsai , Orr William C , Chen Chien‐Lin
Published: May 2016

Background and Aim

Esophageal infusion of capsaicin‐containing red pepper sauce induced heartburn symptoms in patients with gastroesophageal reflux disease (GERD). We aimed to test the hypothesis whether sleep disturbance modulates esophageal sensitivity to capsaicin infusion in patients with GERD.

Methods

We enrolled 40 patients with their sleep quality measured by the Pittsburg Sleep Quality Index with > 5 indicating sleep disturbance. Esophageal sensation to capsaicin infusion was documented via measures of lag time to initial heartburn perception, heartburn intensity rating, and sensitivity score by esophageal infusion of capsaicin‐containing red pepper sauce. Objective sleep measures were assessed by ambulatory actigraphy.

Results

We found 22 patients with sleep disturbance. The patients with sleep disturbance had shorter lag time to initial heartburn perception (P = 0.03) and greater sensory intensity rating (P = 0.02). The sensitivity score for capsaicin infusion was greater in patients with sleep disturbance when compared with those without sleep disturbance (P = 0.04). Actigraphy measures revealed that patients with sleep disturbance also had poor sleep efficiency (P = 0.04), longer average awakening time (P = 0.03), and greater total activity account (P = 0.04). The lag time for perceiving capsaicin infusion was positively correlated with total sleep time (r = 0.43, P = 0.03).

Conclusions

We have shown that GERD patients with sleep disturbance have significantly enhanced heartburn perception to capsaicin infusion as compared with those with normal sleep. Our findings suggest that sleep disturbance is associated with esophageal hypersensitivity to capsaicin infusion in patients with GERD.
Comparing Prognostic Tools for Cancer Screening: Considerations for Clinical Practice and Performance Assessment
Authors: Pollack Craig Evan , Blackford Amanda L. , Schoenborn Nancy L. , Boyd Cynthia M. , Peairs Kimberly S. , DuGoff Eva H.
Published: May 2016

Objectives

To compare the agreement and rates of cancer screening using four prognostic tools that require different types of clinical information.

Design

Observational retrospective cohort study.

Setting

2009 and 2010 waves of the Medicare Current Beneficiary Survey.

Participants

Adults aged 66–90 with survey and claims data (N = 9,469).

Measurements

Agreement between four indices predicting short‐term (4–5 years) and long‐term (9–10 years) survival; self‐reported breast and prostate cancer screening.

Results

Agreement between the four prognostic tools was high. Pearson correlation coefficients ranged from 0.63 to 0.90 for short‐term survival and 0.68 to 0.94 for long‐term survival. When defining limited short‐term life expectancy as less than 25% chance of surviving 4 or 5 years, all four tools agreed in 96.4% of the sample. All four tools agreed in their placement of participants into limited or not‐limited long‐term life expectancy in 77.1% of participants (<25% chance of surviving 9 or 10 years). Rates of cancer screening were similarly high in individuals with limited long‐term life expectancy regardless of the tool used: greater than 31% for mammographic screening in women and greater than 69% for prostate cancer screening.

Conclusion

There is substantial agreement among different prognostic tools for short‐ and long‐term survival in Medicare beneficiaries. The high rates of cancer screening of individuals with limited life expectancy suggest the importance of incorporating tools into clinical decision‐making.
Drug Utilization and Inappropriate Prescribing in Centenarians
Authors: Hazra Nisha C. , Dregan Alex , Jackson Stephen , Gulliford Martin C.
Published: May 2016

Objectives

To use primary care electronic health records (EHRs) to evaluate prescriptions and inappropriate prescribing in men and women at age 100.

Design

Population‐based cohort study.

Setting

Primary care database in the United Kingdom, 1990 to 2013.

Participants

Individuals reaching the age of 100 between 1990 and 2013 (N = 11,084; n = 8,982 women, n = 2,102 men).

Measurements

Main drug classes prescribed and potentially inappropriate prescribing according to the 2012 American Geriatrics Society Beers Criteria.

Results

At the age of 100, 73% of individuals (79% of women, 54% of men) had received one or more prescription drugs, with a median of 7 (interquartile range 0–12) prescription items. The most frequently prescribed drug classes were cardiovascular (53%), central nervous system (CNS) (53%), and gastrointestinal (47%). Overall, 32% of participants (28% of men, 32% of women) who received drug prescriptions may have received one or more potentially inappropriate prescriptions, with temazepam and amitriptyline being the most frequent. CNS prescriptions were potentially inappropriate in 23% of individuals, and anticholinergic prescriptions were potentially inappropriate in 18% of individuals.

Conclusion

The majority of centenarians are prescribed one or more drug therapies, and the prescription may be inappropriate for up to one‐third of these individuals. Research using EHRs offers opportunities to understand prescribing trends and improve pharmacological care of the oldest adults.
Do Private Firms Invest Differently than Public Firms? Taking Cues from the Natural Gas Industry
Authors: GILJE ERIK P. , TAILLARD JEROME P.
Published: May 2016

We study how listing status affects investment behavior. Theory offers competing hypotheses on how listing‐related frictions affect investment decisions. We use detailed data on 74,670 individual projects in the U.S. natural gas industry to show that private firms respond less than public firms to changes in investment opportunities. Private firms adjust drilling activity for low capital‐intensity investments. However, they do not increase drilling in response to new capital‐intensive growth opportunities. Instead, they sell these projects to public firms. Our evidence suggests that differences in access to external capital are important in explaining the investment behavior of public and private firms.
Embryonic stem cells markers Oct4 and Nanog correlate with perineural invasion in human salivary gland mucoepidermoid carcinoma
Authors: Destro Rodrigues Maria Fernanda Setúbal , Sedassari Bruno Tavares , Esteves Carina Magalhães , de Andrade Nathália Paiva , Altemani Albina , de Sousa Suzana Cantanhede Orsini Machado , Nunes Fabio Daumas
Published: May 2016

Background

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and is successfully treated by surgery and radiation. However, some patients have recurrent tumours and in these cases, few treatments options are available. Cancer stem cells (CSC) have been observed and isolated from different solid tumours based on the expression of stem cell markers. These cells are associated with tumour initiation, progression as well as treatment resistance. In this study, the expression of stem cell markers CD44, Bmi1, Oct4 and Nanog was evaluated in non‐neoplastic salivary tissue and in MEC.

Methods

Twenty‐eight samples of MEC and their corresponding non‐neoplastic salivary tissue were examined by immunohistochemistry and the stem cell markers expression was correlated with histological and clinical parameters.

Results

CD44 was expressed in the membrane of serous and mucous acini as well as in the ductal cells in normal gland tissue. Bmi1, Oct4 and Nanog were mainly expressed in ductal structures. In MEC, CD44 and Bmi1 showed strong expression in all types of neoplastic cells and both markers revealed intense expression in tumour invasive front. Oct4 and Nanog protein expression was associated with desmoplasia and perineural invasion. Only Oct4 positive tumours were associated with dissociative growth pattern and committed margins.

Conclusion

The stem cell markers CD44, Bmi1, Oct4 and Nanog are frequently expressed in MEC in relation to normal salivary gland and Oct4 and Nanog expression may contribute to aggressiveness and worst prognosis in MEC patients.
Evaluation of Crosses Between Two Geographic Populations of Native Chinese and Introduced Thai Spotted Ivory Shell, Babylonia areolata, in Southern China
Authors: Lü Wengang , Ke Caihuan , Fu Jingqiang , You Weiwei , Luo Xuan , Huang Miaoqin , Yu Jinjin , Li Weidong , Shen Minghui
Published: May 2016

In the present study, intraspecific crossing experiments between Chinese (H) and Thai populations (T) of Babylonia areolata were conducted by using a complete diallel design (H, T, TH, and HT). A total of 45 pedigreed families were obtained and cultured under the same environmental conditions. Positive heterosis was observed for many developmental parameters and shell sizes for most stages from juvenile to adult. Hatching and metamorphosis occurred significantly earlier in the hybrid (HT) than in the parent groups and a crossed group (TH). Rate of metamorphosis was also higher in HT than in the other three groups. Heterosis in shell length and body weight of the crossed group (HT) from the nursery and grow‐out stage to harvest time was high and significantly different from the H, T, and TH groups. For mortality rate from juvenile to adult, total and average heterosis of the crossed group (TH) was positive and significantly different from H, T, and HT. The results of the present study show that intraspecies crosses can be a potentially useful way to increase the economic traits for B. areolata and thus provide a promising method for genetic improvement of the species as a new aquaculture stock in southern China.
Exposure and analysis of microparticles embedded in silica aerogel keystones using NF3‐mediated electron beam–induced etching and energy‐dispersive X‐ray spectroscopy
Authors: Martin Aiden A. , Lin Ting , Toth Milos , Westphal Andrew J. , Vicenzi Edward P. , Beeman Jeffrey , Silver Eric H.
Published: May 2016

In 2006, NASA's Stardust spacecraft delivered to Earth dust particles collected from the coma of comet 81P/Wild 2, with the goal of furthering the understanding of solar system formation. Stardust cometary samples were collected in a low‐density, nanoporous silica aerogel making their study technically challenging. This article demonstrates the identification, exposure, and elemental composition analysis of particles analogous to those collected by NASA's Stardust mission using in‐situ SEM techniques. Backscattered electron imaging is shown by experimental observation and Monte Carlo simulation to be suitable for locating particles of a range of sizes relevant to Stardust (down to submicron diameters) embedded within silica aerogel. Selective removal of the silica aerogel encapsulating an embedded particle is performed by cryogenic NF3‐mediated electron beam–induced etching. The porous, low‐density nature of the aerogel results in an enhanced etch rate compared with solid material, making it an effective, nonmechanical method for the exposure of particles. After exposure, elemental composition of the particle was analyzed by energy‐dispersive X‐ray spectroscopy using a high spectral resolution microcalorimeter. Signals from fluorine contamination are shown to correspond to nonremoved silica aerogel and only in residual concentrations.
Ries Bunte Breccia revisited: Indications for the presence of water in Itzing and Otting drill cores and implications for the emplacement process
Authors: Pietrek Alexa , Kenkmann Thomas
Published: May 2016

We reassessed two drill cores of the Bunte Breccia deposits of the Ries crater, Germany. The objectives of our study were the documentation of evidence for water in the Bunte Breccia, the evaluation of how that water influenced the emplacement processes, and from which preimpact water reservoir it was derived. The Bunte Breccia in both cores can be structured into a basal layer composed mainly of local substrate material, overlain by texturally and compositionally diverse, crater‐derived breccia units. The basal layer is composed of the youngest sediments (Tertiary clays and Upper Jurassic limestone) and has a razor‐sharp boundary to the upper breccia units, which are composed of older rocks of Upper Jurassic to Upper Triassic age. Sparse material exchange occurred between the basal layer and the rest of the Bunte Breccia. Fluids predominantly came from the Tertiary and the Upper Triassic sandstone formation. In the basal layer, Tertiary clays were subjected to intense, ductile deformation, indicating saturation with water. This suggests that water was mixed into the matrix, creating a fluidized basal layer with a strong shear localization. In the upper units, Upper Triassic sandstones are intensely deformed by granular flow. The texture requires that the rocks were disaggregated into granular sand. Vaporization of pore water probably aided fragmentation of these rocks. In the Otting core, hot suevite (T > 600 °C) covered the Bunte Breccia shortly after its emplacement. Vertically oriented gas escape pipes in suevite partly emanate directly at the contact to the Bunte Breccia. They indicate that the Bunte Breccia contained a substantial amount of water in the upper part that was vaporized and escaped through these vents.