bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of critical residues for transport activity of Acr3p, the Saccharomyces cerevisiae As(III)/H+ antiporter
Authors: Markowska Katarzyna , Maciaszczyk‐Dziubinska Ewa , Migocka Magdalena , Wawrzycka Donata , Wysocki Robert
Published: June 2015

Acr3p is an As(III)/H+ antiporter from Saccharomyces cerevisiae belonging to the bile/arsenite/riboflavin transporter superfamily. We have previously found that Cys151 located in the middle of the fourth transmembrane segment (TM4) is critical for antiport activity, suggesting that As(III) might interact with a thiol group during the translocation process. In order to identify functionally important residues involved in As(III)/H+ exchange, we performed a systematic alanine‐replacement analysis of charged/polar and aromatic residues that are conserved in the Acr3 family and located in putative transmembrane segments. Nine residues (Asn117, Trp130, Arg150, Trp158, Asn176, Arg230, Tyr290, Phe345, Asn351) were found to be critical for proper folding and trafficking of Acr3p to the plasma membrane. In addition, we found that replacement of highly conserved Phe266 (TM7), Phe352 (TM9), Glu353 (TM9) and Glu380 (TM10) with Ala abolished transport activity of Acr3p, while mutation of Ser349 (TM9) to Ala significantly reduced the As(III)/H+ exchange, suggesting an important role of these residues in the transport mechanism. Detailed mutational analysis of Glu353 and Glu380 revealed that the negatively charged residues located in the middle of transmembrane segments TM9 and TM10 are crucial for antiport activity. We also discuss a hypothetical model of the Acr3p transport mechanism.
Binding, internalization and fate of Huntingtin Exon1 fibrillar assemblies in mitotic and nonmitotic neuroblastoma cells
Authors: Ruiz‐Arlandis G. , Pieri L. , Bousset L. , Melki R.
Published: June 2015

Aims

The aggregation of Huntingtin (HTT) protein and of its moiety encoded by its Exon1 (HTTExon1) into fibrillar structures inside neurons is the molecular hallmark of Huntington's disease. Prion‐like transmission of these aggregates between cells has been demonstrated. The cell‐to‐cell transmission mechanisms of these protein aggregates and the susceptibility of different kinds of neuronal cells to these toxic assemblies still need assessment.

Methods

Here, we documented the binding to and internalization by differentiated and undifferentiated neuroblastoma cells of exogenous fibrillar HTTExon1 and polyglutamine (polyQ) polypeptides containing the same number of glutamines. We assessed the contribution of endocytosis to fibrillar HTTExon1 uptake, their intracellular localization and fate.

Results

We observed that undifferentiated neuroblastoma cells were more susceptible to fibrillar HTTExon1 and polyQ than their differentiated counterparts. Furthermore, we demonstrated that exogenous HTTExon1 aggregates are mainly taken up by endocytosis and directed to lysosomal compartments in both mitotic and quiescent cells.

Conclusions

These data suggest that the rates of endocytic processes that differ in mitotic and quiescent cells strongly impact the uptake of exogenous HTTExon1 and polyQ fibrils. This may be either the consequence of distinct metabolisms or distributions of specific protein partners for amyloid‐like assemblies at the surface of highly dividing versus quiescent cells. Our results highlight the importance of endocytic processes in the internalization of exogenous HTTExon1 fibrils and suggest that a proportion of those assemblies reach the cytosol where they can amplify by recruiting the endogenous protein after escaping, by yet an unknown process, from the endo‐lysosomal compartments.
The association between quitting smoking and weight gain: a systemic review and meta‐analysis of prospective cohort studies
Authors: Tian J. , Venn A. , Otahal P. , Gall S.
Published: June 2015

This systematic review and meta‐analysis aimed to quantify weight gain after smoking cessation and the difference in weight gain between quitters and continuing smokers. Five electronic databases were searched before January 2015. Population‐based prospective cohort studies were included if they recorded the weight change of adult smokers from baseline (before smoking cessation) to follow‐up (at least 3 months after cessation). Thirty‐five cohort studies were identified, including 63,403 quitters and 388,432 continuing smokers. The mean weight gain was 4.10 kg (95% confidence interval [CI]: 2.69, 5.51) and body mass index (BMI) gain was 1.14 kg m−2 (95% CI: 0.50, 1.79) among quitters. Compared with continuing smoking, quitting smoking was significantly associated with absolute weight (adjusted mean difference [MD]: 2.61 kg; 95% CI: 1.61, 3.60) and BMI gain (adjusted MD: 0.63 kg m−2; 95% CI: 0.46, 0.80). Subgroup analyses using geographic region found that the difference in weight gain was considerably greater in studies from North America than from Asia. Follow‐up length was identified as a source of heterogeneity, such that studies with longer follow‐up showed greater difference in weight gain. Effective strategies are needed to encourage smokers to quit irrespective of potential weight gain and to help quitters avoid excess weight gain.
N‐acetylcysteine interferes with the biofilm formation, motility and epiphytic behaviour of Xanthomonas citri subsp. citri
Authors: Picchi S. C. , Takita M. A. , Coletta‐Filho H. D. , Machado M. A. , de Souza A. A.
Published: June 2015

Citrus canker is caused by Xanthomonas citri subsp. citri. Bacterial biofilm formation is important in the development of this disease because it is a factor in epiphytic bacterial survival on leaves and in infection. N‐acetylcysteine (NAC), in addition to having antibacterial properties, reduces biofilm formation by a variety of bacteria and was therefore tested for impairing biofilm formation by X. citri. Copper is currently the antimicrobial compound most commonly applied in agriculture to control citrus canker. Therefore, this study also evaluated a possible synergistic effect between NAC and copper to improve the strategy for controlling this phytopathogen. NAC was found to decrease biofilm formation, the production of extracellular polysaccharides and bacterial stickiness. Motility was also affected in the presence of NAC. The best combination of NAC and copper for controlling X. citri was application of NAC followed by copper 48 h later. The concentrations of 6 mg mL−1 of NAC and 3·5 μg mL−1 of copper were able to kill X. citri. NAC inhibited the epiphytic behaviour of X. citri on leaves, altering cell growth and the bacterial ability to form biofilms. The addition of copper to cells previously treated with NAC enhanced its bactericidal activity. In conclusion, NAC has antibacterial properties against X. citri, interfering with bacterial growth, motility and biofilm formation. Under epiphytic conditions, NAC made the cells more susceptible to copper by affecting X. citri biofilm formation. This study opens new possibilities for the use of NAC in combination with copper, possibly resulting in more sustainable management of citrus canker.
Formation Age and Evolution Time Span of the Koktokay No. 3 Pegmatite, Altai, NW China: Evidence from U–Pb Zircon and 40Ar–39Ar Muscovite Ages
Authors: Zhou Qifeng , Qin Kezhang , Tang Dongmei , Tian Ye , Cao Mingjian , Wang Chunlong
Published: June 2015

The Koktokay No. 3 pegmatite is the largest Li–Be–Nb–Ta–Cs pegmatitic rare‐metal deposit of the Chinese Altai orogenic belt, and is famous for its concentric ring zonation pattern (nine internal zones). However, the formation age and evolution time span have been controversial. Here, we present the results of LA‐ICP–MS zircon U–Pb dating and muscovite 40Ar–39Ar dating. Four groups of zircon U–Pb ages (∼210 Ma, ∼193–198 Ma, ∼186–187 Ma and ∼172 Ma) for Zones II, V, VI, VII, and VIII, and a weighed mean 206Pb/238U age of 965 ± 11 Ma for Zone IV are identified. Also, Zones II, IV, and VI have muscovite 40Ar–39Ar plateau ages of 179.7 ± 1.1 Ma, 182.1 ± 1.0 Ma, and 181.8 ± 1.1 Ma, respectively. Considering previous U–Pb age studies (Zones I, V, and VII), the ages of emplacement, Li mineralization peak, hydrothermal stage of the No. 3 pegmatite are in ranges of 193–198 Ma, 184–187 Ma and 172–175 Ma, with weighted mean 206Pb–238U ages of 194.8 ± 2.3 Ma, 186.6 ± 1.3 Ma and 173.1 ± 3.9 Ma, respectively. The No. 3 pegmatite formed in the early Jurassic. The results of xenocrysts suggest that there is another pegmatite forming event of around 210 Ma in the mining district and the old zircon U–Pb ages imply that Neoproterozoic crustal rocks pertain to sources of the No. 3 pegmatite. Including the previous muscovite 40Ar–39Ar age studies (Zones I and V), a cooling age range of 177–182 Ma is considered as the time of hydrothermal stage and end of formation. The evolution process of the No. 3 pegmatite lasted 16 Ma. Therein, the magmatic stage continued for 9–11 Myr and the magmatic–hydrothermal transition and hydrothermal stages were sustained at 5–7 Ma. These time spans are long because of huge scale, cupola shape, large formation depth, and complex internal zoning patterns and formation processes. Considering some pegmatite dikes in the Chinese Altai, there is an early Jurassic pegmatite forming event.
Sulfur Isotope Variations of Metallic Ore Deposits in the Gyeongsang Basin, South Korea
Authors: Jo Jaeguk , Shin Dongbok
Published: June 2015

Many metallic ore deposits of the Late Cretaceous to Early Tertiary periods are distributed in the Gyeongsang Basin. Previous and newly analyzed sulfur isotope data of 309 sulfide samples from 56 ore deposits were reviewed to discuss the genetic characteristics in relation to granitoid rocks. The metallogenic provinces of the Gyeongsang Basin are divided into the Au–Ag(–Cu–Pb–Zn) province in the western basin where the sedimentary rocks of the Shindong and Hayang groups are distributed, Pb–Zn(–Au–Ag–Cu), Cu–Pb–Zn(–Au–Ag), and Fe–W(–Mo) province in the central basin where the volcanic rocks of the Yucheon Group are dominant, and Cu(–Mo–W–Fe) province in the southeastern basin where both sedimentary rocks of the Hayang Group and Tertiary volcanic rocks are present. Average sulfur isotope compositions of the ore deposits show high tendencies ranging from 2.2 to 11.7‰ (average 5.4‰) in the Pb–Zn(–Au–Ag–Cu) province, −0.7 to 11.5‰ (average 4.6‰) in the Cu–Pb–Zn(–Au–Ag) province, and 3.7 to 11.4‰ (average 7.5‰) in the Fe–W(–Mo) province in relation to magnetite‐series granitoids, whereas they are low in the Au–Ag(–Cu–Pb–Zn) province in relation to ilmenite‐series granitoids, ranging from −2.9 to 5.7‰ (average 1.7‰). In the Cu(–Mo–W–Fe) province δ34S values are intermediate ranging from 0.3 to 7.7‰ (average 3.6‰) and locally high δ34S values are likely attributable to sulfur derived from the Tertiary volcanic rocks during hydrothermal alteration through faults commonly developed in this region. Magma originated by the partial melting of the 34S‐enriched oceanic plate intruded into the volcanic rocks and formed magnetite‐series granitoids in the central basin, which contributed to high δ34S values of the metallic deposits. Conversely, ilmenite‐series granitoids were formed by assimilation of sedimentary rocks rich in organic sulfur that influenced the low δ34S values of the deposits in the western and southeastern provinces.
Persistent Poverty and Children's Cognitive Development: Evidence from the UK Millennium Cohort Study
Authors: Dickerson Andrew , Popli Gurleen K.
Published: June 2015

We use data from the four sweeps of the UK Millennium Cohort Study of children born at the turn of the 21st century to document the effect that poverty, and in particular persistent poverty, has on their cognitive development in their early years. Using structural equation modelling, we show that children born into poverty have significantly lower test scores at age 3, age 5 and age 7 years, and that continually living in poverty in their early years has a cumulative negative effect on their cognitive development. For children who are persistently in poverty throughout their early years, their cognitive development test scores at age 7 years are almost 20 percentile ranks lower than children who have never experienced poverty, even after controlling for a wide range of background characteristics and parental investment.
Variable Grid Method: An Intuitive Approach for Simultaneously Quantifying and Visualizing Spatial Data and Uncertainty
Authors: Bauer Jennifer R. , Rose Kelly
Published: June 2015

Efforts to develop applications and methods that effectively quantify and communicate uncertainty associated with spatial data remains a focus within many scientific communities. However, the inherent complexity of uncertainty makes it difficult to define, characterize, and represent. Frequently, the products of spatial and spatio‐temporal data are presented without a clear explanation of the inherent uncertainty underlying the data. As uses and applications for spatial data and their products continues to increase, so does the importance for utilizing reliable approaches to effectively communicate spatial data along with their inherent uncertainties. To address this need, the Variable Grid Method (VGM) was developed as an intuitive approach that simultaneously communicates both spatial patterns and trends and the uncertainty associated with data or their analyses. This article details the VGM approach and demonstrates the utility of the VGM to provide critical information about the relationship between uncertainty and spatial data, necessary to support the increasing utilization of spatial information for a wide range of research and other needs.
Projection, Recognition, and Pictorial Diversity
Authors: Inkpin Andrew
Published: June 2015

This article focuses on the difficulty for a general theory of depiction of providing a notion of pictorial content that accommodates the full diversity of picture types. The article begins by introducing two basic models of pictorial content using paradigmatic positions that maximize the ability of the respective models to deal with pictorial diversity. Kulvicki's On Images is interpreted as a generalized projection‐based model which proposes a scene‐centred notion of pictorial content. By contrast, Lopes's aspect‐recognition theory, in Understanding Pictures, is taken to exemplify a recognition‐based model of pictorial content. It is then considered how applicable these two notions of pictorial content are to a spectrum of different picture types (e.g., photography, painting, caricature), highlighting differences between mechanically produced and “freehand” pictures. It is shown that while the projection‐based and recognition‐based models are each required for some picture types, neither model can be applied over the whole spectrum of diverse picture types. This, it is argued, has the far‐reaching consequence that neither the projection model nor the recognition model, nor any unitary combination of the two, can provide the basis for a theory of depiction applying to all pictures.
Inhibitors of Protein Translocation Across the ER Membrane
Authors: Kalies Kai‐Uwe , Römisch Karin
Published: June 2015

Protein translocation into the endoplasmic reticulum (ER) constitutes the first step of protein secretion. ER protein import is essential in all eukaryotic cells and is particularly critical in fast‐growing tumour cells. Thus, the process can serve as target both for potential cancer drugs and for bacterial virulence factors. Inhibitors of protein transport across the ER membrane range from broad‐spectrum to highly substrate‐specific and can interfere with virtually any stage of this multistep process, and even with transport of endocytosed antigens into the cytosol for cross‐presentation.
Did Globalisation Influence Credit Market Deregulation?
Authors: Eppinger Peter , Potrafke Niklas
Published: June 2015

We investigate whether globalisation influenced credit market deregulation over the period 1970–2010. Globalisation is measured by the KOF indices of globalisation. Credit market deregulation is measured by the credit market freedom indicators of the Fraser Institute. The results from both cross‐sectional and panel regressions using ordinary least squares indicate a positive correlation between globalisation and credit market deregulation. We account for reverse causality using predicted trade openness as an instrumental variable and show that this approach gives rise to different conclusions. Two‐stage least squares estimations do not show that globalisation had a causal influence on credit market deregulation.
Remittances and Financial Access: Is There Really a Link and for Whom? Evidence from Mexican Household Data
Authors: Ambrosius Christian
Published: June 2015

In policy discussions, it has frequently been claimed that migrants' remittances could function as a ‘catalyst’ for financial access among receiving households. This paper provides empirical evidence on this hypothesis from Mexico, a major receiver of remittances worldwide. Using the Mexican Family Life Survey panel (MxFLS) for 2002 and 2005, the results from the fixed effects logit model show that receiving remittances is strongly correlated with the ownership of savings accounts and to a limited degree with the availability of borrowing options. Effects are particularly important for microfinance institutions, and more important for rural households compared to urban households.
Alopecia areata universalis in a dog
Authors: Ginel Pedro J. , Blanco Beatriz , Pérez‐Aranda María , Zafra Rafael , Mozos Elena
Published: June 2015

Background

Alopecia areata is a T‐cell mediated autoimmune disease that occurs in humans and various other mammalian species. When the disease progresses to total alopecia it is defined as alopecia areata universalis (AAU), although this outcome has only been described in humans.

Hypothesis/objectives

To describe a case of canine alopecia areata universalis and its clinical outcome after 22 months of follow‐up.

Animal

A 9‐year‐old intact male cross‐breed hunting dog was presented with generalized and complete noninflammatory alopecia of 12–14 months duration.

Methods

Clinical examination; histopathological and immunohistochemical examination of skin biopsies.

Results

There was loss of all body hair including eyelashes and vibrissae. The histopathological and immunohistochemical findings supported a diagnosis of long‐standing alopecia areata. Treatment with oral ciclosporin was associated with hair regrowth but muzzle hair, most eyelashes and whiskers were still lacking after 17 months of therapy.

Conclusions and clinical importance

To the best of the author's knowledge this is the first documented case of canine AAU. The clinical and histopathological features were consistent with a diagnosis of AAU as defined in humans. Treatment with oral ciclosporin resulted in near complete resolution of the alopecia, but after 5 months without treatment the alopecia did not relapse and spontaneous resolution cannot be ruled out.
Pipeline Inspection Gauge Position Estimation Using Inertial Measurement Unit, Odometer, and a Set of Reference Stations
Authors: Chowdhury Md Sheruzzaman , Abdel-Hafez Mamoun F.
Published: June 2015

This paper presents a low-cost methodology to estimate the position of a pipeline inspection gauge (PIG). The environment in which the PIG navigates is inside the thick walls of a metallic pipeline, where it is not possible to receive a global positioning system (GPS) signal. As a consequence, it is necessary to use other means of navigation. A technique is presented in the paper that uses an inertial measurement unit (IMU), a speedometer, and a set of reference stations. A Kalman filter is used to fuse the measurements from the IMU, the speedometer, and the reference stations. The reference stations, with known GPS coordinates, are installed for every set interval to correct the PIG’s state estimate from the errors that accumulate due to the integration of the IMU measurements. The paper presents three scenarios. These scenarios differ in the way the update step of the Kalman filter is performed. Experimental results are presented along with a 100-run Monte Carlo test to verify the estimator’s consistency.
Fatigue Life Prediction Based on Probabilistic Fracture Mechanics: Case Study of Automotive Parts
Authors: Yazdanipour Mahboubeh , Pourgol-Mohammad Mohammad , Choupani Naghd-Ali , Yazdani Mojtaba
Published: June 2015

This paper studies the stochastic behavior of fatigue crack growth analytically and empirically by employing basic models in fracture mechanics. The research estimates the crack growth rate probabilistically, quantifies the uncertainty of probabilistic models under fatigue loading in automotive parts, and applies the simulations on W319 aluminum alloy, which has vast applications in automotive components’ products. Walker and Forman correlations are used in the paper. The deterministic simulations of these models are verified with afgrow code and validated experimentally with fatigue data of W319 aluminum. Then, the models are treated probabilistically by considering the models’ parameters stochastic. Monte Carlo (MC) simulation is employed to investigate the models under stochastic conditions. The paper is quantifies the propagation of uncertainty with calculating the standard deviations of crack lengths via cycles. The proposed procedure is useful for selecting a proper probabilistic fatigue crack growth model in specific applications and can be used in future fatigue studies not only in the automotive industry but also in other critical fields, to obtain more reliable conclusions.
How Does Concrete Affect Evaporation of Cryogenic Liquids: Evaluating Liquefied Natural Gas Plant Safety
Authors: Ibarreta Alfonso , Hart Ryan J. , Ponchaut Nicolas , Morrison Delmar “Trey” , Kytömaa Harri
Published: June 2015

With the impending natural gas boom in the United States, many companies are pursuing Department of Energy (DOE) approval for exporting liquefied natural gas (LNG), which is a cryogenic liquid. The next decade also promises to demonstrate growth in LNG-fueled fleets of vehicles and marine vessels, as well as growth in other natural gas uses. The future expansion in the LNG infrastructure will lead to an increased focus on managing the risks associated with spills of LNG. Risk analysis involving LNG spill scenarios and their consequences requires determining the size of resulting ignitable flammable vapor clouds. This in turn depends strongly on the rate of evaporation of the spilled LNG. The evaporation of a cryogenic LNG spill (and thus the flammable vapor cloud hazard) can be quite a complex process, and it is primarily controlled by the rate of spreading of the pool and by the transient conductive heat transfer from the ground to the spilled liquid. Radiative and convective heat transfer are also present, but the conductive heat transfer rate dominates in the evaporation of a cryogenic liquid spilled into a trench or sump initially at ambient temperature. The time-dependent evaporation rate can be calculated using a variety of models, such as the built-in model in PHAST Det Norske Veritas (DNV) or other proprietary models that account for pool spreading, heat conduction within the substrate, and phase change. Trenches and sumps used to contain LNG spills are normally lined with various types of concrete, including insulated or aerated concrete. The authors have found that for a cryogenic liquid, the choice of thermal properties for concrete can greatly affect the source term. This paper presents a sensitivity study of the effects of substrate properties on the evaporation rate of LNG. The study will look at the dependence for a range of sump diameters. The PHAST model results will be compared to results obtained using an in-house shallow water equation (SWE) liquid propagation and heat transfer model. The results of the paper will provide guidance for the selection of substrate properties during modeling as well as a comparison of the relative evaporation rates expected for different surfaces, such as regular concrete and insulated concrete.
Efficient imaging of midbrain nuclei using inverse double‐echo steady‐state acquisition a)
Authors: Wu Ming‐Long , Chang Hing‐Chiu , Chao Tzu‐Cheng , Chen Nan‐Kuei
Published: June 2015

Purpose:

Imaging of midbrain nuclei using T2‐ or T2*‐weighted MRI often entails long echo time, leading to long scan time. In this study, an inverse double‐echo steady‐state (iDESS) technique is proposed for efficiently depicting midbrain nuclei.

Methods:

Thirteen healthy subjects participated in this study. iDESS was performed along with two sets of T2*‐weighted spoiled gradient‐echo images (SPGR1, with scan time identical to iDESS and SPGR2, using clinical scanning parameters as a reference standard) for comparison. Generation of iDESS composite images combining two echo signals was optimized for maximal contrast‐to‐noise ratio (CNR) between the red nuclei and surrounding tissues. Signal‐to‐noise ratios (SNRs) were calculated from the occipital lobe. Comparison was also made using phase‐enhanced images as in standard susceptibility‐weighted imaging (SWI).

Results:

The iDESS images present significantly higher SNR efficiency (171.3) than SPGR1 (158.7, p = 0.013) and SPGR2 (95.5, p < 10−8). iDESS CNR efficiency (19.2) is also significantly greater than SPGR1 (6.9, p < 10−6) and SPGR2 (14.3, p = 0.0016). Compared with DESS, iDESS provides further advantage on enhanced phase information and hence improved contrast on SWI‐processed images.

Conclusions:

iDESS efficiently depicts midbrain nuclei with improved CNR efficiency, increased SNR efficiency, and reduced scan time and is less prone to susceptibility signal loss from air‐tissue interfaces.
Vigorous Physical Activity and All-Cause Mortality: A Story That Got Lost in Translation
Authors: Ding Ding , Gebel Klaus , Freeman Becky , Bauman Adrian E.
Published: June 2015

Media reporting of published research findings can increase the profile and reach of new scientific findings. Dissemination is an important part of research, and media reporting can catalyze this process. In many areas, including health-related research, policymakers often rely on the media for information and guidance. Furthermore, media reports can influence the scientific community and clinicians.1·2 However, despite the potential beneficial role as a bridge between scientists and the public, misleading information can cause controversy, confusion, and even harm.3
Model Fidelity and Students’ Responses to an Authenticated Unit of Cooperative Learning
Authors: Casey Ashley , Goodyear Victoria A. , Dyson Ben P.
Published: June 2015

A wealth of school-based interventions report on students’ positive responses to the use of models-based practice in physical education. However, research that examines the effectiveness of models-based practice rarely reports on the fidelity of implementation i.e., when all of the characteristics of a model are implemented. The purpose of this study was to explore model fidelity in the use of the Cooperative Learning model. Action research and systematic observation (using the Cooperative Learning Validation Tool which acknowledged the observation of key characteristics of the model) were used to confirm model fidelity. Consequently, the themes which emerged from the data analysis of could be directly linked to the authentic use of Cooperative Learning context. The paper concludes by arguing that when reporting on findings from empirical research on the use of Cooperative Learning we need to adopt a more robust approach in determining—through rigor and quality of research—the authenticity of implementation.
Physical Education Teacher Educator’s Perceptions Toward and Understanding of K-12 Online Physical Education
Authors: Daum David N. , Woods Amelia M.
Published: June 2015

K-12 online physical education (OLPE) is as an educational opportunity in at least 30 states in the US (NASPE, 2006; 2010; 2012). The purpose of this study was to examine physical education teacher educators’ perceptions toward and understanding of K-12 OLPE. Bandura’s Social Cognitive Theory (1986) served as the theoretical framework for this study. Data were collected utilizing semistructured open-ended interviews. Participants (N = 25) were current physical education teacher education (PETE) faculty members at universities granting bachelor’s degrees in physical education certification. Participants believed that NASPE (2004) National Physical Education Standards could be met online, except for Standard 1, which relates to motor skill competency. Participants were almost unanimous in their beliefs that OLPE should not be designed for elementary-aged children, but is viable at the high school level. This study provided initial insight into PETE faculty members’ knowledge about and perceptions of K-12 OLPE, however additional research is warranted.
The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage
Authors: Tu Chi-Chiang , Zhong Yan , Nguyen Louis , Tsai Aaron , Sridevi Priya , Tarn Woan-Yuh , Wang Jean Y. J.
Published: June 2015

DNA damage triggers the biogenesis of some miRNAs through the activity of the kinase ABL.
Multitasking around the clock
Authors: Kiberstis Paula A.
Published: June 2015

A transcription factor that controls both circadian rhythms and metabolism does so through different genomic mechanisms.
Making cardiomyocytes
Authors: Purnell Beverly A.
Published: June 2015

Identification of the committed cardiomyoblast that retains proliferative potential may inform cardiac regenerative therapeutics.
Vitamin B
12
contributes to acne by affecting the skin microbiota
Authors: Colmone Angela
Published: June 2015

Vitamin B
12
stimulates the transcription of genes that promote inflammation from the skin microbiota.
Competing for stomata
Authors: VanHook Annalisa M.
Published: June 2015

Two structurally related peptides compete for binding to the same receptor to control the density of stomata on leaves.
ER trap for blood pressure control
Authors: Gough Nancy R.
Published: June 2015

Formation of a disulfide bond between an ER chaperone and an angiotensin II–metabolizing enzyme reduces blood pressure.
The Ribosomal S10 Protein Is a General Target for Decreased Tigecycline Susceptibility
Authors: Beabout Kathryn , Hammerstrom Troy G. , Perez Anisha Maria , Magalhães Bárbara Freitas , Prater Amy G. , Clements Thomas P. , Arias Cesar A. , Saxer Gerda , Shamoo Yousif
Published: June 2015

Tigecycline is a translational inhibitor with efficacy against a wide range of pathogens. Using experimental evolution, we adapted
Acinetobacter baumannii
,
Enterococcus faecium
,
Escherichia coli
, and
Staphylococcus aureus
to growth in elevated tigecycline concentrations. At the end of adaptation, 35 out of 47 replicate populations had clones with a mutation in
rpsJ
, the gene that encodes the ribosomal S10 protein. To validate the role of mutations in
rpsJ
in conferring tigecycline resistance, we showed that mutation of
rpsJ
alone in
Enterococcus faecalis
was sufficient to increase the tigecycline MIC to the clinical breakpoint of 0.5 μg/ml. Importantly, we also report the first identification of
rpsJ
mutations associated with decreased tigecycline susceptibility in
A. baumannii
,
E. coli
, and
S. aureus
. The identified S10 mutations across both Gram-positive and -negative species cluster in the vertex of an extended loop that is located near the tigecycline-binding pocket within the 16S rRNA. These data indicate that S10 is a general target of tigecycline adaptation and a relevant marker for detecting reduced susceptibility in both Gram-positive and -negative pathogens.
Resistance to the Antimicrobial Agent Fosmidomycin and an FR900098 Prodrug through Mutations in the Deoxyxylulose Phosphate Reductoisomerase Gene (
dxr
)
Authors: Armstrong Christopher M. , Meyers David J. , Imlay Leah S. , Freel Meyers Caren , Odom Audrey R.
Published: June 2015

There is a pressing need for new antimicrobial therapies to combat globally important drug-resistant human pathogens, including
Plasmodium falciparum
malarial parasites,
Mycobacterium tuberculosis
, and Gram-negative bacteria, including
Escherichia coli
. These organisms all possess the essential methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, which is not found in humans. The first dedicated enzyme of the MEP pathway, 1-deoxy-
d
-xylulose 5-phosphate reductoisomerase (Dxr), is inhibited by the phosphonic acid antibiotic fosmidomycin and its analogs, including the
N
-acetyl analog FR900098 and the phosphoryl analog fosfoxacin. In order to identify mutations in
dxr
that confer resistance to these drugs, a library of
E. coli
dxr
mutants was screened at lethal fosmidomycin doses. The most resistant allele (with the S222T mutation) alters the fosmidomycin-binding site of Dxr. The expression of this resistant allele increases bacterial resistance to fosmidomycin and other fosmidomycin analogs by 10-fold. These observations confirm that the primary cellular target of fosmidomycin is Dxr. Furthermore, cell lines expressing Dxr-S222T will be a powerful tool to confirm the mechanisms of action of future fosmidomycin analogs.
Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients
Authors: Cojutti Piergiorgio , Maximova Natalia , Pea Federico
Published: June 2015

This study explored the pharmacokinetics and the pharmacodynamics of continuous-infusion meropenem in a population of pediatric hematopoietic stem cell transplant (HSCT) patients who underwent therapeutic drug monitoring. The relationship between meropenem clearance (CLM) and estimated creatinine clearance (CLCR) was assessed by nonlinear regression. A Monte Carlo simulation was performed to investigate the predictive performance of five dosing regimens (15 to 90 mg/kg of body weight/day) for the empirical treatment of severe Gram-negative-related infections in relation to four different categories of renal function. The optimal target was defined as a probability of target attainment (PTA) of ≥90% at steady-state concentration-to-MIC ratios (CSS/MIC) of ≥1 and ≥4 for MICs of up to 8 mg/liter. A total of 21 patients with 44 meropenemCSSwere included. A good relationship between CLMand estimated CLCRwas observed (r2= 0.733). Simulations showed that at an MIC of 2 mg/liter, the administration of continuous-infusion meropenem at doses of 15, 30, 45, and 60 mg/kg/day may achieve a PTA of ≥90% at aCSS/MIC ratio of ≥4 in the CLCRcategories of 40 to <80, 80 to <120, 120 to <200, and 200 to <300 ml/min/1.73 m2, respectively. At an MIC of 8 mg/liter, doses of up to 90 mg/kg/day by continuous infusion may achieve optimal PTA only in the CLCRcategories of 40 to <80 and 80 to <120 ml/min/1.73 m2. Continuous-infusion meropenem at dosages up to 90 mg/kg/day might be effective for optimal treatment of severe Gram-negative-related infections in pediatric HSCT patients, even when caused by carbapenem-resistant pathogens with an MIC of up to 8 mg/liter.
ELQ-300 Prodrugs for Enhanced Delivery and Single-Dose Cure of Malaria
Authors: Miley Galen P. , Pou Sovitj , Winter Rolf , Nilsen Aaron , Li Yuexin , Kelly Jane X. , Stickles Allison M. , Mather Michael W. , Forquer Isaac P. , Pershing April M. , White Karen , Shackleford David , Saunders Jessica , Chen Gong , Ting Li-Min , Kim Kami , Zakharov Lev N. , Donini Cristina , Burrows Jeremy N. , Vaidya Akhil B. , Charman Susan A. , Riscoe Michael K.
Published: June 2015

ELQ-300 is a preclinical candidate that targets the liver and blood stages of
Plasmodium falciparum
, as well as the forms that are crucial to transmission of disease: gametocytes, zygotes, and ookinetes. A significant obstacle to the clinical development of ELQ-300 is related to its physicochemical properties. Its relatively poor aqueous solubility and high crystallinity limit absorption to the degree that only low blood concentrations can be achieved following oral dosing. While these low blood concentrations are sufficient for therapy, the levels are too low to establish an acceptable safety margin required by regulatory agencies for clinical development. One way to address the challenging physicochemical properties of ELQ-300 is through the development of prodrugs. Here, we profile ELQ-337, a bioreversible O-linked carbonate ester prodrug of the parent molecule. At the molar equivalent dose of 3 mg/kg of body weight, the delivery of ELQ-300 from ELQ-337 is enhanced by 3- to 4-fold, reaching a maximum concentration of drug in serum (
C
max
) of 5.9 μM by 6 h after oral administration, and unlike ELQ-300 at any dose, ELQ-337 provides single-dose cures of patent malaria infections in mice at low-single-digit milligram per kilogram doses. Our findings show that the prodrug strategy represents a viable approach to overcome the physicochemical limitations of ELQ-300 to deliver the active drug to the bloodstream at concentrations sufficient for safety and toxicology studies, as well as achieving single-dose cures.
Draft Genome Sequence of Lactobacillus delbrueckii subsp.
bulgaricus
CRL871, a Folate-Producing Strain Isolated from a Northwestern Argentinian Yogurt
Authors: Laiño Jonathan Emiliano , Hebert Elvira María , Savoy de Giori Graciela , LeBlanc Jean Guy
Published: June 2015

Lactobacillus delbrueckii
subsp.
bulgaricus
CRL871 is the first strain of
L. delbrueckii
subsp.
bulgaricus
reported as a folate-producing strain. We report the draft genome sequence of
L. delbrueckii
subsp.
bulgaricus
CRL871 (2,063,981 bp, G+C content of 49.1%). This strain is of great biotechnological importance to the dairy industry because it constitutes an alternative to folic acid fortification.
Evolution of the Immune Response to Chronic Airway Colonization with Aspergillus fumigatus Hyphae
Authors: Urb Mirjam , Snarr Brendan D. , Wojewodka Gabriella , Lehoux Mélanie , Lee Mark J. , Ralph Benjamin , Divangahi Maziar , King Irah L. , McGovern Toby K. , Martin James G. , Fraser Richard , Radzioch Danuta , Sheppard Donald C.
Published: June 2015

Airway colonization by the moldAspergillus fumigatusis common in patients with underlying lung disease and is associated with chronic airway inflammation. Studies probing the inflammatory response to colonization withA. fumigatushyphae have been hampered by the lack of a model of chronic colonization in immunocompetent mice. By infecting mice intratracheally with conidia embedded in agar beads (Af beads), we have established anin vivomodel to study the natural history of airway colonization with liveA. fumigatushyphae. Histopathological examination and galactomannan assay of lung homogenates demonstrated that hyphae exited beads and persisted in the lungs of mice up to 28 days postinfection without invasive disease. Fungal lesions within the airways were surrounded by a robust neutrophilic inflammatory reaction and peribronchial infiltration of lymphocytes. Whole-lung cytokine analysis from Af bead-infected mice revealed an increase in proinflammatory cytokines and chemokines early in infection. Evidence of a Th2 type response was observed only early in the course of colonization, including increased levels of interleukin-4 (IL-4), elevated IgE levels in serum, and a mild increase in airway responsiveness. Pulmonary T cell subset analysis during infection mirrored these results with an initial transient increase in IL-4-producing CD4+T cells, followed by a rise in IL-17 and Foxp3+cells by day 14. These results provide the first report of the evolution of the immune response toA. fumigatushyphal colonization.
How Biofilms Evade Host Defenses
Authors: Roilides Emmanuel , Simitsopoulou Maria , Katragkou Aspasia , Walsh Thomas J.
Published: June 2015

The steps involved during the biofilm growth cycle include attachment to a substrate followed by more permanent adherence of the microorganisms, microcolony arrangement, and cell detachment required for the dissemination of single or clustered cells to other organ systems. Various methods have been developed for biofilm detection and quantitation. Biofilm-producing microorganisms can be detected in tissue culture plates, using silicone tubes and staining methods, and by visual assessment using scanning electron microscopy or confocal scanning laser microscopy. Quantitative measurement of biofilm growth is determined by using methods that include dry cell weight assays, colony-forming-unit counting, DNA quantification, or XTT 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide reduction assay. Upon infection, innate immune defense strategies are able to establish an immediate response through effector mechanisms mediated by immune cells, receptors, and several humoral factors. We present an overview of the life cycle of biofilms and their diversity, detection methods for biofilm development, and host immune responses to pathogens. We then focus on current concepts in bacterial and fungal biofilm immune evasion mechanisms. This appears to be of particular importance because the use of host immune responses may represent a novel therapeutic approach against biofilms.
Modeling the Epidemiology of Cholera to Prevent Disease Transmission in Developing Countries
Authors: Mukandavire Zindoga , Morris J. Glenn
Published: June 2015

Cholera remains an important global cause of morbidity and mortality, which is capable of causing periodic epidemic disease. A number of mathematical models have been developed to help in understanding the dynamics of cholera outbreaks and for use as a tool in planning interventions, including vaccination campaigns. We have explored the utility of models in assessing the spread of cholera in the recent epidemics in Zimbabwe and Haiti. In both instances, a mathematical model was formulated and fitted to cumulative cholera cases to estimate the basic reproductive number ℛ
0
, and the partial reproductive numbers reflecting potential differences in environmental-to-human versus human-to-human transmission were quantified. In Zimbabwe, estimated ℛ
0
for the epidemic using aggregated data at the national level was 1.15; in Haiti, it was 1.55. However, when calculated at a provincial/departmental level, estimated basic reproductive numbers were highly heterogeneous, with a range of 1.11 to 2.72 in Zimbabwe and 1.06 to 2.63 in Haiti. Our models suggest that the underlying patterns of cholera transmission varied widely from region to region, with a corresponding variation in the amenability of outbreaks to control measures such as immunization. These data underscore the heterogeneity of transmission dynamics, potentially linked to differences in environment, socio-economic conditions, and cultural practices. They also highlight the potential utility of these types of models in guiding development of public health intervention strategies.
Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study
Authors: Sørgjerd Elin Pettersen , Thorsby Per M , Torjesen Peter A , Skorpen Frank , Kvaløy Kirsti , Grill Valdemar
Published: June 2015

Background

It is well known that anti-GAD (glutamic acid decarboxylase) serves as a marker for development of autoimmune diabetes in adults. On the other hand, the clinical implications of anti-GAD positivity in persistently non-diabetic (PND) adults are poorly elucidated. Our aim was to establish the frequency of anti-GAD in PNDs in an all-population-based cohort from the Nord-Trøndelag health study (HUNT) and to prospectively test for associations with glucose tolerance and thyroid autoimmunity.

Methods

We formed a primary study population (4496 individuals), selected randomly from the age group 20–90 years (50% men/women), who were non-diabetic both at HUNT2 (1995–1997) and HUNT3 (2006–2008). Anti-GAD-positive individuals at HUNT2, together with anti-GAD-negative individuals aged 20–29 years, were retested for anti-GAD positivity at HUNT3. A secondary study population consisted of individuals with type 2 diabetes (T2D, n=349) at HUNT3 who developed diabetes between HUNT2 and HUNT3.

Results

The frequency of anti-GAD positivity in PND was 1.7% (n=76) at HUNT2. Positivity did not associate with gender, family history of diabetes, or glucose levels, but was associated with thyroid-associated autoimmunity (increased frequency of positivity for anti-TPO (thyroid peroxidase), p<0.002). HLA-DQA1/DQB1, a risk haplotype for autoimmunity, was also associated with anti-GAD positivity in PND. The incidence of anti-GAD positivity was low (0.4%) in the subsample of individuals who were anti-GAD negative in HUNT2. Anti-GAD positivity in PNDs was frequently evanescent, with 54% losing, usually low-grade, positivity between HUNT2 and HUNT3. An evanescent state of autoimmunity as assessed by anti-GAD positivity during “pre-diabetes” in individuals later diagnosed with T2D could, however, not be affirmed.

Conclusions

Anti-GAD positivity in PND is associated with HLA risk haplotypes and thyroid autoimmunity but not with clinical parameters of diabetes. Fleeting anti-GAD positivity is common; however, results do not support the notion of a history of autoimmunity in T2D in the present cohort.
Association of endothelial lipase gene−384A/C with coronary artery disease in Han Chinese people
Authors: Xie Liang , Sun Yan , Tong Yu , Liu Ying , Deng Ying
Published: June 2015

Objectives

The endothelial lipase gene (LIPG) is one of the important genes in the metabolism of high-density lipoprotein cholesterol (HDL-C) and may be involved in the pathogenesis of coronary artery disease (CAD).

Materials and methods

To investigate the relationship between the common single nucleotide polymorphisms (SNPs) 584C/T (rs2000813) and −384A/C (rs3813082) in theLIPGgene and CAD, allele and genotype frequencies of the two SNPs were analysed in 287 Chinese patients with CAD and 367 controls by the high-resolution melting curve (HRM) method.

Results

For 584C/T, no significant difference in polymorphic distribution was observed between patients and controls. However, the frequencies of allele C (20.2% vs 15%, p=0.013, OR=1.437, 95% CI 1.078 to 1.915) at −384A/C were significantly increased in patients compared with controls. Haplotype analysis also showed that haplotype CT (12.37% vs 8.72%, p=0.035, OR=1.478, 95% CI 1.034 to 2.112) was significantly higher in patients compared with controls.

Conclusions

These results suggested that the SNP −384A/C in the LIPG gene may be associated with risk for CAD and theLIPGgene may play a role in CAD in the Han Chinese.