bluuebunny/crossref_metadata_2025 huggingface dataset:
Are sample sizes of randomized clinical trials in rheumatoid arthritis too large?
Authors: Celik Selda , Yazici Yusuf , Yazici Hasan
Published: September 2014

Objective

We had the impression that randomized clinical trials (RCTs) frequently over enrolled patients. Thus, we surveyed power calculations in publications of RCTs of biologics in rheumatoid arthritis (RA) to assess over enrollment.

Methods

A PubMed search identified 40 reports of original RCTs testing the efficacy of infliximab, etanercept, adalimumab, abatacept, rituximab and tocilizumab in patients with RA. As a first analysis, based on a two equal arms study with an alpha error of 0·05 and a power of 80% and of 90%, recalculation of the sample size was performed using the primary outcome results. In the second analysis, only those studies with equal number of patients in both arms and also in which all elements of a power calculation were given, were considered. New sample sizes were calculated based on the presented power elements in the related publications.

Results

In the first analysis, when we assigned a power of 80% and of 90%, 32 of 40 (80%) studies enrolled more than required number of patients, with a mean 131 ± 147 (SD), and 31 of 40 (78%) studies having had enrolled extra patients, with a mean 121 ± 147 (SD) in their treatment arms, respectively. Eleven studies qualified for the second analysis. There were still more patients with a mean of 48 ± 30 (SD) extra patients enrolled in the treatment arms.

Conclusion

Most RCTs in RA enrol more patients than needed. This is costly and has the immediate consequence of exposing needless number of patients to potential harm.
Transition issues for children with diffuse cortical malformations, multifocal postnatal lesions, (infectious and traumatic) and Lennox–Gastaut and similar syndromes
Authors: Camfield Peter R. , Bahi‐Buisson Nadia , Trinka Eugen
Published: September 2014

Patients with epilepsy may have diffuse, serious brain disorders including genetically determined, multilobar malformations, traumatic brain injury, encephalitis and meningitis, and the many causes of Lennox‐Gastaut syndrome. Transition to adult care needs to consider concomitant intellectual disability, refractory epilepsy, underlying cause, and other nonneurologic but significant problems, especially for genetic etiologies. Adult epilepsy care coupled with dedicated primary/family care is essential. A multidisciplinary setting may be optimal to address the many issues of clinical care, decision making, custody, and ongoing supervision.
Transition to adult life in the monogenic epilepsies
Authors: Scheffer Ingrid E. , Dravet Charlotte
Published: September 2014

There are many monogenic disorders associated with epilepsy that begin in childhood and persist into adult life. Each of these disorders raises specific issues for transition, in addition to common issues facing this group of patients as they move from pediatric to adult care. Such comorbidities include psychiatric and movement disorders. Epileptic encephalopathies may be caused by monogenic disorders, with Dravet syndrome being the best characterized. Although some patients have a relatively good adult outcome, others have persisting severe epilepsy complicated by autistic spectrum disorder and problems with gait. When reevaluating a patient as they transition to adult care, a thorough reconsideration of the genetic etiology of their epilepsy should be performed. This should be followed by genetic counseling for the patient and their family members.
Forest ecosystem respiration estimated from eddy covariance and chamber measurements under high turbulence and substantial tree mortality from bark beetles
Authors: Speckman Heather N. , Frank John M. , Bradford John B. , Miles Brianna L. , Massman William J. , Parton William J. , Ryan Michael G.
Published: September 2014

Eddy covariance nighttime fluxes are uncertain due to potential measurement biases. Many studies report eddy covariance nighttime flux lower than flux from extrapolated chamber measurements, despite corrections for low turbulence. We compared eddy covariance and chamber estimates of ecosystem respiration at the GLEES Ameriflux site over seven growing seasons under high turbulence [summer night mean friction velocity (u*) = 0.7 m s−1], during which bark beetles killed or infested 85% of the aboveground respiring biomass. Chamber‐based estimates of ecosystem respiration during the growth season, developed from foliage, wood, and soil CO2 efflux measurements, declined 35% after 85% of the forest basal area had been killed or impaired by bark beetles (from 7.1 ± 0.22 μmol m−2 s−1 in 2005 to 4.6 ± 0.16 μmol m−2 s−1 in 2011). Soil efflux remained at ~3.3 μmol m−2 s−1 throughout the mortality, while the loss of live wood and foliage and their respiration drove the decline of the chamber estimate. Eddy covariance estimates of fluxes at night remained constant over the same period, ~3.0 μmol m−2 s−1 for both 2005 (intact forest) and 2011 (85% basal area killed or impaired). Eddy covariance fluxes were lower than chamber estimates of ecosystem respiration (60% lower in 2005, and 32% in 2011), but the mean night estimates from the two techniques were correlated within a year (r2 from 0.18 to 0.60). The difference between the two techniques was not the result of inadequate turbulence, because the results were robust to a u* filter of >0.7 m s−1. The decline in the average seasonal difference between the two techniques was strongly correlated with overstory leaf area (r2 = 0.92). The discrepancy between methods of respiration estimation should be resolved to have confidence in ecosystem carbon flux estimates.
Pollen‐based quantitative reconstructions of Holocene regional vegetation cover (plant‐functional types and land‐cover types) in Europe suitable for climate modelling
Authors: Trondman A.‐K. , Gaillard M.‐J. , Mazier F. , Sugita S. , Fyfe R. , Nielsen A. B. , Twiddle C. , Barratt P. , Birks H. J. B. , Bjune A. E. , Björkman L. , Broström A. , Caseldine C. , David R. , Dodson J. , Dörfler W. , Fischer E. , van Geel B. , Giesecke T. , Hultberg T. , Kalnina L. , Kangur M. , van der Knaap P. , Koff T. , Kuneš P. , Lagerås P. , Latałowa M. , Lechterbeck J. , Leroyer C. , Leydet M. , Lindbladh M. , Marquer L. , Mitchell F. J. G. , Odgaard B. V. , Peglar S. M. , Persson T. , Poska A. , Rösch M. , Seppä H. , Veski S. , Wick L.
Published: September 2014

We present quantitative reconstructions of regional vegetation cover in north‐western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1° × 1° spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. TheREVEALSmodel was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant‐functional types and three land‐cover types [evergreen trees, summer‐green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6kbpand modern time in theREVEALSestimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2kbpis significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer‐green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or asREVEALSestimates of tree cover. For instance, whenPinusis dominant overPiceaas pollen percentages,Piceais dominant overPinusasREVEALSestimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover–climate interactions, biodiversity and human resources.
Long‐term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands
Authors: Bighetti Bruna B. , Assis Gerson F. d. , Vieira Danilo C. , Violato Natalia M. , Cestari Tania M. , Taga Rumio , Bosqueiro José R. , Rafacho Alex
Published: September 2014

Glucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long‐term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P < 0.05). DEX rat islets secreted more insulin in response to glucose (P < 0.05). DEX rats had significant reductions in the masses of the parotid (29%) and submandibular (16%) glands (P < 0.05) that was associated with reduced salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P < 0.05). The total number of acinar cells was increased in the submandibular glands of the DEX rats (P < 0.05) but not in the parotid glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long‐term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland‐specific response to GCs. Our data emphasize that GC‐based therapies and insulin‐resistant states have a negative impact on salivary gland homeostasis.
Intended and Unintended Pregnancies Worldwide in 2012 and Recent Trends
Authors: Sedgh Gilda , Singh Susheela , Hussain Rubina
Published: September 2014

Periodic estimation of the incidence of global unintended pregnancy can help demonstrate the need for and impact of family planning programs. We draw upon multiple sources of data to estimate pregnancy incidence by intention status and outcome at worldwide, regional, and subregional levels in 2012 and to assess recent trends using previously published estimates for 2008 and 1995. We find that 213 million pregnancies occurred in 2012, up slightly from 211 million in 2008. The global pregnancy rate decreased only slightly from 2008 to 2012, after declining substantially between 1995 and 2008. Eighty‐five million pregnancies, representing 40 percent of all pregnancies, were unintended in 2012. Of these, 50 percent ended in abortion, 13 percent ended in miscarriage, and 38 percent resulted in an unplanned birth. The unintended pregnancy rate continued to decline in Africa and in the Latin America and Caribbean region. If the aims of the London Summit on Family Planning are carried out, the incidence of unwanted and mistimed pregnancies should decline in the coming years.
Couples' Unmet Need for Family Planning in Three West African Countries
Authors: Pearson Erin , Becker Stan
Published: September 2014

Unmet need for family planning is typically calculated for currently married women, but excluding husbands may result in misleading estimates of couples' unmet need. This study builds on previous work and proposes a method of calculating couples' unmet need for family planning based on spouses' independent fertility intentions. We analyze Demographic and Health Survey data from couples from three West African countries—Benin, Burkina Faso, and Mali. We find that fewer than half of couples having any unmet need had concordant unmet need (41–49 percent). A similar percentage of couples had wife‐only unmet need (33–40 percent). A smaller percentage had husband‐only unmet need (15–23 percent). Calculating unmet need based only on women's fertility intentions overestimates concordant unmet need. Additionally, that approximately 15–23 percent of couples have husband‐only unmet need suggests that men could be an entry point for contraceptive use for more couples than at present. To calculate husbands' unmet need, population‐based surveys should consider collecting the necessary data consistently.
Creating internal conductivity in dry biological SEM samples by a simple vapour treatment
Authors: ENSIKAT H.‐J. , WEIGEND M.
Published: September 2014

Internal sample conductivity in scanning electron microscopy can be a valuable alternative to metal coating. Proton conductivity may be used for this purpose. Many solid materials with active hydrogen atoms, such as hydrogen‐ and ammonium‐salts, organic acids, and even ice, are protonic conductors or semiconductors. Here we present a method to generate proton conductivity in dry biological materials. A simple treatment with hydrogen chloride gas or hydrochloric acid vapour for a few minutes provides sufficient conductivity for many samples. After a removal of excess hydrogen chloride vapour with a vacuum desiccator, the objects may be examined in the SEM without metal coating. The use of internally conductive samples extends the range of easy‐to‐perform SEM preparation techniques. It is advantageous for material contrast imaging of uncoated samples, and it can be used in combination with metal coating to enhance conductivity on difficult samples with complex overlapping surfaces, where simple metal coating does not reliably eliminate charging problems.
Prolactin Regulation of Kisspeptin Neurones in the Mouse Brain and its Role in the Lactation‐Induced Suppression of Kisspeptin Expression
Authors: Brown R. S. E. , Herbison A. E. , Grattan D. R.
Published: September 2014

Hyperprolactinaemia is a major cause of infertility in both males and females, although the mechanism by which prolactin inhibits the reproductive axis is not clear. The aim of the present study was to test the hypothesis that elevated prolactin causes suppression of kisspeptin expression in the hypothalamus, resulting in reduced release of gonadotrophin‐releasing hormone (GnRH) and consequent infertility. In oestrogen‐treated ovariectomised mice, chronic prolactin‐treatment prevented the rise in luteinising hormone (LH) seen in vehicle‐treated mice. Kiss1 mRNA was significantly suppressed in both the rostral periventricular region of the third ventricle (RP3V) and arcuate nucleus after prolactin treatment. Exogenous prolactin treatment induced phosphorylated signal transducer and activator of transcription 5 (pSTAT5) in kisspeptin neurones, and suppression of endogenous prolactin using bromocriptine reduced levels of pSTAT5 in kisspeptin neurones, suggesting that prolactin acts directly on kisspeptin neurones. By contrast, fewer than 1% of GnRH neurones expressed pSTAT5 in either dioestrous or lactating mice. As reported previously, there was significant suppression of kisspeptin mRNA and protein in the RP3V on day 7 of lactation, although not in the arcuate nucleus. Bromocriptine treatment significantly increased Kiss1 mRNA expression in the RP3V, although not to dioestrous levels. Unilateral thelectomy, aiming to eliminate sensory inputs from nipples on one side of the body, failed to alter the reduction in the number of kisspeptin neurones observed in the RP3V. These data demonstrate that chronic prolactin administration suppressed serum LH, and reduced Kiss1 mRNA levels in both the RP3V and arcuate nucleus, consistent with the hypothesis that prolactin‐induced suppression of kisspeptin secretion might mediate the inhibitory effects of prolactin on GnRH secretion. During lactation, however, the suppression of Kiss1 mRNA in the RP3V was only partially reversed by the administration of bromocriptine to block elevated levels of prolactin, suggesting that, although elevated prolactin contributes to lactational anovulation, additional non‐neural factors must also contribute to the lactation‐induced suppression of kisspeptin neurones.
The relationship between a night's sleep and subsequent daytime functioning in older poor and good sleepers
Authors: Smith Rashelle A. , Lack Leon C. , Lovato Nicole , Wright Helen
Published: September 2014

Those suffering insomnia symptoms generally report daytime impairments. However, research has not assessed whether this relationship holds on a nightly basis, despite the strongly held belief that a night of poor sleep impairs mood and functioning the following day. The objective of this study was to test this relationship in a group of older poor sleepers with insomnia symptoms compared with good sleepers. This study utilized a within‐subjects design to investigate day‐to‐day subjective daytime functioning and its relation to the previous night's sleep. Seventeen older individuals (mean age: 67.5 years) were identified with a retrospective questionnaire and 2 weeks of sleep–wake diary to have poor sleep consistent with insomnia. Seventeen good sleepers (mean age: 67.8 years) were selected using the same measures. Participants reported their beliefs about sleep and daytime functioning on the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS‐16). One week later they commenced a 14‐day period of sleep–wake diaries and concurrent responses to a modified Daytime Insomnia Symptom Scale (DISS). Results showed significant night‐to‐day covariation between sleep efficiency and daytime functioning for individuals with poor sleep (r = 0.34), but not for good sleepers (r = 0.08). Those poor sleepers who held this covariation belief most strongly were those who subsequently showed this night‐to‐day relationship the most strongly (r = 0.56). This was not true for good sleepers. For those suffering insomnia, these findings demonstrate their belief that a poor sleep is followed by an impaired daytime, consistent with their experience.
Is there a species spectrum within the world‐wide leaf economics spectrum? Major variations in leaf functional traits in the Mediterranean sclerophyll Quercus ilex
Authors: Niinemets Ülo
Published: September 2014

The leaf economics spectrum is a general concept describing coordinated variation in foliage structural, chemical and physiological traits across resource gradients. Yet, within this concept, the role of within‐species variation, including ecotypic and plastic variation components, has been largely neglected. This study hypothesized that there is a within‐species economics spectrum within the general spectrum in the evergreen sclerophyll Quercus ilex which dominates low resource ecosystems over an exceptionally wide range. An extensive database of foliage traits covering the full species range was constructed, and improved filtering algorithms were developed. Standardized data filtering was deemed absolutely essential as additional variation sources can result in trait variation of 10–300%, blurring the broad relationships. Strong trait variation, c. two‐fold for most traits to up to almost an order of magnitude, was uncovered. Although the Q. ilex spectrum is part of the general spectrum, within‐species trait and climatic relationships in this species partly differed from the overall spectrum. Contrary to world‐wide trends, Q. ilex does not necessarily have a low nitrogen content per mass and can increase photosynthetic capacity with increasing foliage robustness. This study argues that the within‐species economics spectrum needs to be considered in regional‐ to biome‐level analyses.
Insights from the cold transcriptome of Physcomitrella patens: global specialization pattern of conserved transcriptional regulators and identification of orphan genes involved in cold acclimation
Authors: Beike Anna K. , Lang Daniel , Zimmer Andreas D. , Wüst Florian , Trautmann Danika , Wiedemann Gertrud , Beyer Peter , Decker Eva L. , Reski Ralf
Published: September 2014

The whole‐genome transcriptomic cold stress response of the moss Physcomitrella patens was analyzed and correlated with phenotypic and metabolic changes.

Based on time‐series microarray experiments and quantitative real‐time polymerase chain reaction, we characterized the transcriptomic changes related to early stress signaling and the initiation of cold acclimation. Transcription‐associated protein (TAP)‐encoding genes of P. patens and Arabidopsis thaliana were classified using generalized linear models. Physiological responses were monitored with pulse‐amplitude‐modulated fluorometry, high‐performance liquid chromatography and targeted high‐performance mass spectrometry.

The transcript levels of 3220 genes were significantly affected by cold. Comparative classification revealed a global specialization of TAP families, a transcript accumulation of transcriptional regulators of the stimulus/stress response and a transcript decline of developmental regulators.

Although transcripts of the intermediate to later response are from evolutionarily conserved genes, the early response is dominated by species‐specific genes. These orphan genes may encode as yet unknown acclimation processes.
Insect and pathogen attack and resistance in maize and its wild ancestors, the teosintes
Authors: de Lange Elvira S. , Balmer Dirk , Mauch‐Mani Brigitte , Turlings Ted C. J.
Published: September 2014

Maize (Zea mays ssp. mays) is one of the most important crops worldwide and there are many reports in the literature on its constitutive and inducible defenses against pathogens and insects. However, research on its wild ancestors, the teosintes, with respect to resistance against these antagonists is limited. Here, we review what is known about the different arthropods and microbes that are associated with maize and teosintes in Mexico and Central America, the area of origin, and evaluate the plants' mechanisms of resistance against biotic stresses. Teosintes appear to have greater resistance against a number of pests than their cultivated counterpart. We therefore highlight the need to study the teosintes in order to identify resistance traits that can be improved in maize. As teosintes are at risk of becoming extinct, there is a need to protect their germplasm for future generations.
Histamine H4 receptor in oral lichen planus
Authors: Salem A , Al‐Samadi A , Stegajev V , Stark H , Häyrinen‐Immonen R , Ainola M , Hietanen J , Konttinen YT
Published: September 2014

Objectives

Oral lichen planus (OLP) is an autoimmune disease characterized by a band‐like T‐cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high‐affinity histamine H4 receptors (H4Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T‐cell cytokines.

Materials and Methods

Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real‐time polymerase chain reaction of tissue samples and cytokine‐stimulated cultured SCC‐25 and primary human oral keratinocytes.

Results

H4R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4R agonist at nanomolar levels led to a rapid internalization of H4Rs, whereas high histamine concentration and interferon‐γ decreased HRH4‐gene transcripts.

Conclusion

Healthy oral epithelial cells are equipped with H4R, which displays a uniform staining pattern in a MC‐independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4R. Cell culture experiments suggest a rapid H4R stimulation‐dependent receptor internalization and a slow cytokine‐driven decrease in H4R synthesis. H4R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.
Modulation of IL‐33/ST2‐TIR and TLR Signalling Pathway by Fingolimod and Analogues in Immune Cells
Authors: Rüger K. , Ottenlinger F. , Schröder M. , Živković A. , Stark H. , Pfeilschifter J. M. , Radeke H. H.
Published: September 2014

For the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell‐based confocal assay and IL‐33/ST2‐TIR Th2‐like response with ST2‐transduced EL4‐6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR‐enhanced antigen presentation assay with OVA‐TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy‐derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720‐P. The IL‐33/ST2‐TIR Th2‐like response in ST2‐EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA‐TCRtg LPS/TLR‐enhanced spleen cell assay, we found that fingolimod inhibited both IL‐17 and IFN‐γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune‐modulating properties of fingolimod, including interference with a prototypical Th2 response via IL‐33/ST2‐TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR‐activated and antigen‐dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives.
Optimal and Robust Designs for Estimating the Concentration Curve and the AUC
Authors: Belouni Mohamad , Benhenni Karim
Published: September 2014

The problem of interest is to estimate the concentration curve and the area under the curve (AUC) by estimating the parameters of a linear regression model with an autocorrelated error process. We introduce a simple linear unbiased estimator of the concentration curve and the AUC. We show that this estimator constructed from a sampling design generated by an appropriate density is asymptotically optimal in the sense that it has exactly the same asymptotic performance as the best linear unbiased estimator. Moreover, we prove that the optimal design is robust with respect to a minimax criterion. When repeated observations are available, this estimator is consistent and has an asymptotic normal distribution. Finally, a simulated annealing algorithm is applied to a pharmacokinetic model with correlated errors.
Using genic sequence capture in combination with a syntenic pseudo genome to map a deletion mutant in a wheat species
Authors: Gardiner Laura‐Jayne , Gawroński Piotr , Olohan Lisa , Schnurbusch Thorsten , Hall Neil , Hall Anthony
Published: September 2014

Mapping‐by‐sequencing analyses have largely required a complete reference sequence and employed whole genome re‐sequencing. In species such as wheat, no finished genome reference sequence is available. Additionally, because of its large genome size (17 Gb), re‐sequencing at sufficient depth of coverage is not practical. Here, we extend the utility of mapping by sequencing, developing a bespoke pipeline and algorithm to map an early‐flowering locus in einkorn wheat (Triticum monococcum L.) that is closely related to the bread wheat genome A progenitor. We have developed a genomic enrichment approach using the gene‐rich regions of hexaploid bread wheat to design a 110‐Mbp NimbleGen SeqCap EZ in solution capture probe set, representing the majority of genes in wheat. Here, we use the capture probe set to enrich and sequence an F2 mapping population of the mutant. The mutant locus was identified in T. monococcum, which lacks a complete genome reference sequence, by mapping the enriched data set onto pseudo‐chromosomes derived from the capture probe target sequence, with a long‐range order of genes based on synteny of wheat with Brachypodium distachyon. Using this approach we are able to map the region and identify a set of deleted genes within the interval.
Detection of Draft Tube Surge and Erosive Blade Cavitation in a Full-Scale Francis Turbine
Authors: Escaler Xavier , Ekanger Jarle V. , Francke Håkon H. , Kjeldsen Morten , Nielsen Torbjørn K.
Published: September 2014

A full-scale Francis turbine has been experimentally investigated over its full range of operation to detect draft tube swirling flows and cavitation. The unit is of interest due to the presence of severe pressure fluctuations at part load and of advanced blade suction-side cavitation erosion. Moreover, the turbine has a particular combination of guide vanes (20) to runner blades (15) that makes it prone to significant rotor-stator interaction (RSI). For that, a complete measurement system of dynamic pressures, temperatures, vibrations, and acoustic emissions has been setup with the corresponding transducers mounted at selected sensitive locations. The experiments have comprised an efficiency measurement, a signal transmissibility evaluation, and the recording of the raw signals at high sampling rates. Signal processing methods for demodulation, peak power estimation, and cross correlation have also been applied. As a result, draft tube pressure fluctuations have been detected around the Rheingans frequency for low loads and at 4% of the rotating frequency for high loads. Moreover, maximum turbine guide bearing acoustic emissions have been measured at full load with amplitude modulations at both the guide vane passing frequency and the draft tube surge frequency.
Physical Activity Monitoring in Extremely Obese Adolescents From the Teen-LABORATORIES Study
Authors: Jeffreys Renee M. , Inge Thomas H. , Jenkins Todd M. , King Wendy C. , Oruc Vedran , Douglas Andrew D. , Bray Molly S.
Published: September 2014

Background:

The accuracy of physical activity (PA) monitors to discriminate between PA, sedentary behavior, and nonwear in extremely obese (EO) adolescents is unknown.

Methods:

Twenty-five subjects (9 male/16 female; age = 16.5 ± 2.0 y; BMI = 51 ± 8 kg/m2) wore 3 activity monitors (StepWatch [SAM], Actical [AC], Actiheart [AH]) during a 400-m walk test (400MWT), 2 standardized PA bouts of varying duration, and 1 sedentary bout.

Results:

For the 400MWT, percent error between observed and monitor-recorded steps was 5.5 ± 7.1% and 82.1 ± 38.6% for the SAM and AC steps, respectively (observed vs. SAM steps: −17.2 ± 22.2 steps; observed vs. AC steps: −264.5 ± 124.8 steps). All activity monitors were able to differentiate between PA and sedentary bouts, but only SAM steps and AH heart rate were significantly different between sedentary behavior and nonwear (P < .001). For all monitors, sedentary behavior was characterized by bouts of zero steps/counts punctuated by intermittent activity steps/counts; nonwear was represented almost exclusively by zero steps/counts.

Conclusion:

Of all monitors tested, the SAM was most accurate in terms of counting steps and differentiating levels of PA and thus, most appropriate for EO adolescents. The ability to accurately characterize PA intensity in EO adolescents critically depends on activity monitor selection.
Intracellular Vibrio parahaemolyticus Escapes the Vacuole and Establishes a Replicative Niche in the Cytosol of Epithelial Cells
Authors: de Souza Santos Marcela , Orth Kim
Published: September 2014

Vibrio parahaemolyticus
is a globally disseminated Gram-negative marine bacterium and the leading cause of seafood-borne acute gastroenteritis. Pathogenic bacterial isolates encode two type III secretion systems (T3SS), with the second system (T3SS2) considered the main virulence factor in mammalian hosts. For many decades,
V. parahaemolyticus
has been studied as an exclusively extracellular bacterium. However, the recent characterization of the T3SS2 effector protein VopC has suggested that this pathogen has the ability to invade, survive, and replicate within epithelial cells. Herein, we characterize this intracellular lifestyle in detail. We show that following internalization,
V. parahaemolyticus
is contained in vacuoles that develop into early endosomes, which subsequently mature into late endosomes.
V. parahaemolyticus
then escapes into the cytoplasm prior to vacuolar fusion with lysosomes. Vacuolar acidification is an important trigger for this escape. The cytoplasm serves as the pathogen’s primary intracellular replicative niche; cytosolic replication is rapid and robust, with cells often containing over 150 bacteria by the time of cell lysis. These results show how
V. parahaemolyticus
successfully establishes an intracellular lifestyle that could contribute to its survival and dissemination during infection.

IMPORTANCE
The marine bacterium
V. parahaemolyticus
is the leading cause worldwide of seafood-borne acute gastroenteritis. For decades, the pathogen has been studied exclusively as an extracellular bacterium. However, recent results have revealed the pathogen’s ability to invade and replicate within host cells. The present study is the first characterization of the
V. parahaemolyticus
’ intracellular lifestyle. Upon internalization,
V. parahaemolyticus
is contained in a vacuole that would in the normal course of events ultimately fuse with a lysosome, degrading the vacuole’s contents. The bacterium subverts this pathway, escaping into the cytoplasm prior to lysosomal fusion. Once in the cytoplasm, it replicates prolifically. Our study provides new insights into the strategies used by this globally disseminated pathogen to survive and proliferate within its host.
The Plant Pathogen Xanthomonas campestris pv.
campestris
Exploits
N
-Acetylglucosamine during Infection
Authors: Boulanger Alice , Zischek Claudine , Lautier Martine , Jamet Stevie , Rival Pauline , Carrère Sébastien , Arlat Matthieu , Lauber Emmanuelle
Published: September 2014

N
-Acetylglucosamine (GlcNAc), the main component of chitin and a major constituent of bacterial peptidoglycan, is present only in trace amounts in plants, in contrast to the huge amount of various sugars that compose the polysaccharides of the plant cell wall. Thus, GlcNAc has not previously been considered a substrate exploited by phytopathogenic bacteria during plant infection.
Xanthomonas campestris
pv.
campestris
, the causal agent of black rot disease of
Brassica
plants, expresses a carbohydrate utilization system devoted to GlcNAc exploitation. In addition to genes involved in GlcNAc catabolism, this system codes for four TonB-dependent outer membrane transporters (TBDTs) and eight glycoside hydrolases. Expression of all these genes is under the control of GlcNAc.
In vitro
experiments showed that
X. campestris
pv.
campestris
exploits chitooligosaccharides, and there is indirect evidence that during the early stationary phase,
X. campestris
pv.
campestris
recycles bacterium-derived peptidoglycan/muropeptides. Results obtained also suggest that during plant infection and during growth in cabbage xylem sap,
X. campestris
pv.
campestris
encounters and metabolizes plant-derived GlcNAc-containing molecules. Specific TBDTs seem to be preferentially involved in the consumption of all these plant-, fungus- and bacterium-derived GlcNAc-containing molecules. This is the first evidence of GlcNAc consumption during infection by a phytopathogenic bacterium. Interestingly,
N
-glycans from plant
N
-glycosylated proteins are proposed to be substrates for glycoside hydrolases belonging to the
X. campestris
pv.
campestris
GlcNAc exploitation system. This observation extends the range of sources of GlcNAc metabolized by phytopathogenic bacteria during their life cycle.

IMPORTANCE
Despite the central role of
N
-acetylglucosamine (GlcNAc) in nature, there is no evidence that phytopathogenic bacteria metabolize this compound during plant infection. Results obtained here suggest that
Xanthomonas campestris
pv.
campestris
, the causal agent of black rot disease on
Brassica
, encounters and metabolizes GlcNAc
in planta
and
in vitro
. Active and specific outer membrane transporters belonging to the TonB-dependent transporters family are proposed to import GlcNAc-containing complex molecules from the host, from the bacterium, and/or from the environment, and bacterial glycoside hydrolases induced by GlcNAc participate in their degradation. Our results extend the range of sources of GlcNAc metabolized by this phytopathogenic bacterium during its life cycle to include chitooligosaccharides that could originate from fungi or insects present in the plant environment, muropeptides leached during peptidoglycan recycling and bacterial lysis, and
N-
glycans from plant
N
-glycosylated proteins present in the plant cell wall as well as in xylem sap.
Relaxed Substrate Specificity Leads to Extensive tRNA Mischarging by Streptococcus pneumoniae Class I and Class II Aminoacyl-tRNA Synthetases
Authors: Shepherd Jennifer , Ibba Michael
Published: September 2014

Aminoacyl-tRNA synthetases provide the first step in protein synthesis quality control by discriminating cognate from noncognate amino acid and tRNA substrates. While substrate specificity is enhanced in many instances by
cis-
and
trans
-editing pathways, it has been revealed that in organisms such as
Streptococcus pneumoniae
some aminoacyl-tRNA synthetases display significant tRNA mischarging activity. To investigate the extent of tRNA mischarging in this pathogen, the aminoacylation profiles of class I isoleucyl-tRNA synthetase (IleRS) and class II lysyl-tRNA synthetase (LysRS) were determined. Pneumococcal IleRS mischarged tRNA
Ile
with both Val, as demonstrated in other bacteria, and Leu in a tRNA sequence-dependent manner. IleRS substrate specificity was achieved in an editing-independent manner, indicating that tRNA mischarging would only be significant under growth conditions where Ile is depleted. Pneumococcal LysRS was found to misaminoacylate tRNA
Lys
with Ala and to a lesser extent Thr and Ser, with mischarging efficiency modulated by the presence of an unusual U4:G69 wobble pair in the acceptor stems of both pneumococcal tRNA
Lys
isoacceptors. Addition of the
trans-
editing factor MurM, which also functions in peptidoglycan synthesis, reduced Ala-tRNA
Lys
production by LysRS, providing evidence for cross talk between the protein synthesis and cell wall biogenesis pathways. Mischarging of tRNA
Lys
by AlaRS was also observed, and this would provide additional potential MurM substrates. More broadly, the extensive mischarging activities now described for a number of
Streptococcus pneumoniae
aminoacyl-tRNA synthetases suggest that adaptive misaminoacylation may contribute significantly to the viability of this pathogen during amino acid starvation.

IMPORTANCE
Streptococcus pneumoniae
is a common causative agent of several debilitating and potentially life-threatening infections, such as pneumonia, meningitis, and infectious endocarditis. Such infections are increasingly difficult to treat due to widespread development of penicillin resistance. High-level penicillin resistance is known to depend in part upon MurM, a protein involved in both aminoacyl-tRNA-dependent synthesis of indirect amino acid cross-linkages within cell wall peptidoglycan and in translation quality control. The involvement of MurM in both protein synthesis and antibiotic resistance identify it as a potential target for the development of new and potent antibiotics for pneumococcal infections. The goals of this work were to identify and characterize
S. pneumoniae
pathways that can synthesize mischarged tRNAs and to relate these activities to expected changes in protein and peptidoglycan biosynthesis during antibiotic and nutritional stress.
Differential effects of STAT proteins on growth hormone-mediated IGF-I gene expression
Authors: Varco-Merth Ben , Rotwein Peter
Published: September 2014

Growth hormone (GH) plays a key role regulating somatic growth and in controlling metabolism and other physiological processes in humans and other animal species. GH acts by binding to the extracellular part of its transmembrane receptor, leading to induction of multiple intracellular signal transduction pathways that culminate in changes in gene and protein expression. A key agent in GH-stimulated growth is the latent transcription factor signal transducer and activator of transcription (STAT) 5B, one of four STAT proteins induced by the GH receptor in cultured cells and in vivo. As shown by genetic and biochemical studies, GH-activated STAT5B promotes transcription of the gene encoding the critical growth peptide, insulin-like growth factor-I (IGF-I), and natural null mutations of STAT5B in humans lead to growth failure accompanied by diminished IGF-I expression. Here we have examined the possibility that other GH-activated STATs can enhance IGF-I gene transcription, and thus potentially contribute to GH-regulated somatic growth. We find that human STAT5A is nearly identical to STAT5B in its biochemical and functional responses to GH but that STAT1 and STAT3 show a weaker profile of in vitro binding to STAT DNA elements from the IGF-I gene than STAT5B, and are less potent inducers of gene transcription through these elements. Taken together, our results offer a molecular explanation for why STAT5B is a key in vivo mediator of GH-activated IGF-I gene transcription and thus of GH-regulated somatic growth.
Theoretical Simulations of Reactive and Nonreactive Scattering of Light Diatomic Molecules from Metal Surfaces: Past, Present, and Future
Authors: Díaz C.
Published: September 2014

In everyday life we are surrounded by surfaces and, therefore, by phenomena involving molecule-surface interactions. Furthermore, the processes of heterogeneous catalysis, which are governed by molecule-surface interactions, are of huge practical importance, because the production of most synthetic compounds involves catalytic processes, which explains the tremendous effort that surface science scientists have invested to understand the basic principles underlying elementary interactions between light molecules and surfaces. This effort was recognized in 2007 with the Nobel prize in chemistry awarded to Gerhard Ertl. Here we revise some of the most relevant studies performed so far in this field. We also point out the major challenges that the surface science community may face in this field in the years to come.
Error Analysis for a Noisy Lacunary Cubic Spline Interpolation and a Simple Noisy Cubic Spline Quasi Interpolation
Authors: Lang Feng-Gong , Xu Xiao-Ping
Published: September 2014

We mainly present the error analysis for two new cubic spline based methods; one is a lacunary interpolation method and the other is a very simple
quasi interpolation method. The new methods are able to reconstruct a function and its first two derivatives from noisy function data. The explicit error bounds for the methods
are given and proved. Numerical tests and comparisons are performed. Numerical results verify the efficiency of our methods.
Studies on the Vertical Distribution of Ticks of Domestic Animals and Their Public Health Importance in Nilgiri Hills and Adjoining Areas of Tamil Nadu State (India)
Authors: Kumar Kaushal , Balakrishnan N. , Sharma Abhay Kumar
Published: September 2014

The Nilgiri hills and adjoining downhill areas provide favourable ecological conditions for the propagation of haematophagous arthropods owing to richness in vegetation and animal activities. A study has been undertaken during 2008–2010 on the distribution and abundance of ticks of domestic animals in seven different biotopes. A total of 3,008 domestic animals were examined in areas ranging from an altitude of 300 to 2200 meters above mean sea level (MSL) of which 1,335 (44.5%) animals were having tick infestation. A total of 6,012 adult and immature ticks belonging to 12 species (11 ixodid and one argasid) were collected. Eleven tick species were collected from Kallar area situated downhill eastern slopes of the Nilgiris followed by Burliar area (7 species) located at higher altitudes. From Masinagudi area near to dense forests and scrub jungles, five species were recorded. However, at higher elevations on the hills, Udhagamandalam area, only one species was recorded. Among various tick species recorded in the study,Boophilus micropluswas distributed in almost all areas surveyed followed byHaemaphysalis spinigeraandRhipicephalus sanguineus. The factors governing their distribution and epidemiological significance in the transmission of various tick-borne diseases of public health importance are discussed.
Immobilization of Lipase on Silver Nanoparticles via Adhesive Polydopamine for Biodiesel Production
Authors: Dumri Kanchana , Hung Anh Dau
Published: September 2014

Biodiesel production technology is competitive in terms of low cost and alternative source of energy which should be not only sustainable but also environmentally friendly. Designing of the lipase immobilization for biodiesel production has a remarkable impact and is still challenging. In this work, biodiesel production from soybean oil was enhanced and facilitated by using a novel biocatalyst consisting of commercial lipase (EC 3.1.1.3), silver nanoparticles, and polydopamine. Silver nanoparticles (AgNPs) were synthesized with a size range of 10–20 nm. Polydopamine (PD) was delivered by the self-polymerization of dopamine in 10 mM Tris-HCl pH 8.5 and simultaneously coated the AgNPs to form a PD/AgNPs complex. Lipase was immobilized on the PD/AgNPs complex surface via covalent bonds to form a tailor-made biocatalyst consisting of immobilized lipase/PD/AgNPs complex (LPA). The formation and morphology of each composition were characterized by UV-Vis spectroscopy and scanning electron microscope (SEM). Significantly, gas chromatography analysis showed a remarkable biodiesel production yield of 95% by using the LPA complex at 40°C for 6-hours reaction time, whereas the yield was 86% when using free lyophilized lipase. The LPA complex was apparently reusable after 7 batches and the latter conversion rate of soybean oil was decreased by only 27%.
Resistance Training Exercise Program for Intervention to Enhance Gait Function in Elderly Chronically Ill Patients: Multivariate Multiscale Entropy for Center of Pressure Signal Analysis
Authors: Chen Ming-Shu , Jiang Bernard C.
Published: September 2014

Falls are unpredictable accidents, and the resulting injuries can be serious in the elderly, particularly those with chronic diseases. Regular exercise is recommended to prevent and treat hypertension and other chronic diseases by reducing clinical blood pressure. The “complexity index” (CI), based on multiscale entropy (MSE) algorithm, has been applied in recent studies to show a person’s adaptability to intrinsic and external perturbations and widely used measure of postural sway or stability. The multivariate multiscale entropy (MMSE) was advanced algorithm used to calculate the complexity index (CI) values of the center of pressure (COP) data. In this study, we applied the MSE & MMSE to analyze gait function of 24 elderly, chronically ill patients (44% female; 56% male; mean age,67.56±10.70years) with either cardiovascular disease, diabetes mellitus, or osteoporosis. After a 12-week training program, postural stability measurements showed significant improvements. Our results showed beneficial effects of resistance training, which can be used to improve postural stability in the elderly and indicated that MMSE algorithms to calculate CI of the COP data were superior to the multiscale entropy (MSE) algorithm to identify the sense of balance in the elderly.