bluuebunny/crossref_metadata_2025 huggingface dataset:
Makgeolli: Rapid Production of an Alcoholic Beverage from the Fermentation of Rice
Authors: Kiefer Adam M. , Seney Caryn S. , Lambright Alison L. , Cottrill Kirsten A. , Young Virginia A.
Published: June 2018

Undergraduate microbiology courses offer a perfect opportunity to introduce students to historical food preservation processes that are still in use today. Specifically, food fermentation exercises encourage students to consider other cultures and their food and beverage traditions, in addition to teaching students techniques that can be performed in their own kitchens. In previous semesters of an undergraduate microbiology course we have taught a variety of fermentations through the production of yogurt, sauerkraut, kimchi, and cheese. Student enthusiasm for these food labs led us to explore new fermentations, especially those from other cultures. To this end, a laboratory procedure and worksheets for producing the Korean rice wine makgeolli from fermented rice in the presence of amylase enzyme was developed. Students ferment the rice, bottle the ferment, and those of legal drinking age test the product while completing exercises that challenge them to explore the microbiological concepts of fermentation. Underlying themes of this laboratory activity also include basic concepts of food safety and kitchen cleanliness. The laboratory experiment can be completed in less than two weeks and can be modified easily for students of varying scientific backgrounds. Overall, the intersection of metabolism, food science, cultural diversity, and history excited students and enhanced their understanding of the microbial processes at work in fermentation.
Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines
Authors: Menachery Vineet D. , Gralinski Lisa E. , Mitchell Hugh D. , Dinnon Kenneth H. , Leist Sarah R. , Yount Boyd L. , McAnarney Eileen T. , Graham Rachel L. , Waters Katrina M. , Baric Ralph S.
Published: June 2018

Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2′O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2′O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2′O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.
Match injury incidence during the Super Rugby tournament is high: a prospective cohort study over five seasons involving 93 641 player-hours
Authors: Schwellnus Martin P , Jordaan Esme , Janse van Rensburg Charl , Bayne Helen , Derman Wayne , Readhead Clint , Collins Rob , Kourie Alan , Suter Jason , Strauss Org
Published: June 2018

Objectives

To determine the incidence and nature of injuries in the Super Rugby tournament over a 5-year period.

Methods

482 male professional rugby union players from six South African teams participating in the Super Rugby tournament were studied (1020 player-seasons). Medical staff of participating teams (2012–2016 tournaments) recorded all time loss injuries (total injuries and match injuries) and exposure hours (93 641 total playing hours; 8032 match hours). Injury incidence, injured player proportion, severity (time lost), anatomical location, tissue type and activity/phase during which injury occurred are reported.

Results

The overall incidence of match injuries (per 1000 player-hours; 95% CI) for each year was as follows: 2012 (83.3; 69.4–99.2); 2013 (115.1; 98.7–133.5); 2014 (95.9; 80.8–113.1), 2015 (112.3; 96.6–129.9) and 2016 (93.2; 79.9–107.9). The injured player proportion for each year was as follows: 2012 (54.6%); 2013 (49.4%); 2014 (52.0%); 2015 (50.0%); and 2016 (39.8%). The thigh, knee, head/face and shoulder/clavicle are the most frequently injured locations, and muscle/tendon and joint/ligament injuries account for the majority of injuries. Most injuries (79%) occur in contact situations, in particular during a tackle (54%).

Conclusion

The incidence of match injuries and the injured player proportion in South African teams competing in the Super Rugby tournament is high. Match injury incidence is consistently higher than previously reported for senior male rugby players at elite/professional level. Targeted risk management strategies are therefore needed in the Super Rugby tournament to manage risk of injury.
Development and evaluation of percentile distribution of body weight by gestational week as a tool for gestational weight management: a retrospective study based on hospital routine data
Authors: Zhang Yi , Wang Liping , Yin Chuanmin , Mu Kai , Niu Dayan , Yan Weili
Published: June 2018

Objectives

This study aimed to construct and validate smoothed gestational weight centile curves based on preconception weight status for Chinese pregnant women.

Design

A retrospective study based on hospital routine data

Setting

Hospital prenatal care.

Population

A cohort of pregnant Chinese women with preconception and gestational body weights without maternal or neonatal complications (sample 1, n=2992), and a non-selective independent sample (sample 2, n=7420), were selected from hospital routine data for curve construction and validation.

Study design

Smoothed body weight centile curves for each gestational week were constructed using the LMS method in sample 1. Validation in sample 2 included analysis of agreement between predicted weight at the 38th week and observed values using the Bland–Altman Index. Predictions were also compared with international curves.

Results

Smoothed centile curves of gestational weight for the three preconception body mass index groups showed a similar non-linear increasing trend. The differences between predicted body weights and observed values were 0.66±1.58 kg, 0.14±1.61 kg and −0.54±2.06 kg in the underweight, normal weight and overweight groups, respectively. Bland-Altman Index values were 5.2%, 5.6% and 4.7% in the underweight, normal weight and overweight groups, respectively, with limits of agreement of −2.4~3.8 kg, –3.0~3.3 kg and −4.4~3.4 kg, respectively. These limits of agreement were narrower than those of available international curves.

Conclusion

Body weight percentiles for gestational weeks 0–42 were proposed for underweight, normal weight or overweight Chinese women. These curves could constitute a useful tool for individualised gestational weight management by predicting body weight at a later gestation phase.
Continuity of care with doctors—a matter of life and death? A systematic review of continuity of care and mortality
Authors: Pereira Gray Denis J , Sidaway-Lee Kate , White Eleanor , Thorne Angus , Evans Philip H
Published: June 2018

Objective

Continuity of care is a long-standing feature of healthcare, especially of general practice. It is associated with increased patient satisfaction, increased take-up of health promotion, greater adherence to medical advice and decreased use of hospital services. This review aims to examine whether there is a relationship between the receipt of continuity of doctor care and mortality.

Design

Systematic review without meta-analysis.

Data sources

MEDLINE, Embase and the Web of Science, from 1996 to 2017.

Eligibility criteria for selecting studies

Peer-reviewed primary research articles, published in English which reported measured continuity of care received by patients from any kind of doctor, in any setting, in any country, related to measured mortality of those patients.

Results

Of the 726 articles identified in searches, 22 fulfilled the eligibility criteria. The studies were all cohort or cross-sectional and most adjusted for multiple potential confounding factors. These studies came from nine countries with very different cultures and health systems. We found such heterogeneity of continuity and mortality measurement methods and time frames that it was not possible to combine the results of studies. However, 18 (81.8%) high-quality studies reported statistically significant reductions in mortality, with increased continuity of care. 16 of these were with all-cause mortality. Three others showed no association and one demonstrated mixed results. These significant protective effects occurred with both generalist and specialist doctors.

Conclusions

This first systematic review reveals that increased continuity of care by doctors is associated with lower mortality rates. Although all the evidence is observational, patients across cultural boundaries appear to benefit from continuity of care with both generalist and specialist doctors. Many of these articles called for continuity to be given a higher priority in healthcare planning. Despite substantial, successive, technical advances in medicine, interpersonal factors remain important.

PROSPERO registration number

CRD42016042091.
Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose
Authors: Candotti Daniel , Assennato Sonny Michael , Laperche Syria , Allain Jean-Pierre , Levicnik-Stezinar Snezna
Published: June 2018

Objective

HBV infection by blood components is currently prevented in most developed countries by combining sensitive HBV surface antigen (HBsAg) assays, nucleic acid testing (NAT) and in a few of them antibodies against the HBV core antigen (anti-HBc) screening. HBV transmissions by blood components from three repeat donors tested negative for HBsAg and HBV DNA with a highly sensitive screening test (limit of detection (LOD): 3.4 IU/mL) were investigated.

Design

30 of the 47 recipients of components produced from these three donors were examined. Transfusion transmission was confirmed by phylogenetic analysis of viral sequences obtained from recipients and donors following viral particle concentration.

Results

9 of 31 (29%) recipients were infected: 7 infections were related to 200 mL of fresh frozen plasma and 2 infections to red blood cells containing 20 mL plasma. Transfusion transmission was confirmed by >99% identity of donor/recipient sequences in five cases, probable in three and possible in one. HBV active infection remained unsuspected for 24–57 months in three recipients. Five non-infected recipients carried anti-HBs when transfused. Six patients transfused with platelet concentrates treated with a pathogen reduction method were not infected. These data enabled to revise previous estimate of the minimal infectious dose from approximately 100 to 16 copies (or 3 IU) of HBV DNA.

Conclusions

HBV transfusion transmission from occult HBV infection carrying extremely low viral loads is related to plasma volume transfused and possibly prevented by anti-HBs. HBV blood safety could be further improved by either anti-HBc screening, HBV DNA NAT with a LOD of 0.8 copies/mL (0.15 IU/mL) or pathogen reduction of blood components.
Efficiency of microbially assisted phytoremediation of heavy-metal contaminated soils
Authors: Hrynkiewicz Katarzyna , Złoch Michał , Kowalkowski Tomasz , Baum Christel , Buszewski Bogusław
Published: June 2018

Phytoremediation is the bioremediation of contaminated soils and waters by using plants and their associated microorganisms. Phytoremediation of heavy metal (HM)-contaminated soils is based on immobilization of metals in rhizosphere soil and roots (phytostabilization) and on mobilization, uptake, and transfer of metals into the aboveground plant organs (phytoextraction). In this review, we aimed to (i) discuss the fundamentals, potential, and limitations of plant-associated microorganisms (bacteria and fungi) to increase the efficiency of phytostabilization and phytoextraction of HM-contaminated soils and (ii) describe promising developments and future challenges to expanding their use. Controlled inoculations of plants with growth-promoting microorganisms can significantly increase their root growth, biomass production, and stress tolerance in HM-contaminated soils. A serious weakness of phytoremediation in general is the usually high and difficult to measure expenditure of time for successful completion. The bioconcentration factors (BCFs) and the translocation factors (TFs) are among the most important measures of the efficiency of phytoremediation. However, an overview of BCFs and TFs for a variety of combinations of plants with defined associated microorganisms is lacking. Moreover, the joint evaluation of model systems would allow an improved cost–benefit calculation of microbial inoculations in phytoremediation systems. For this purpose, the use of in vitro model systems is considered to be preferable to field experiments due to the savings in time and costs and the control of environmental conditions. However, the transferability of in vitro data to field conditions is limited. Currently, attention is focused on the use of artificial neural networks, mainly to avoid formulating any complex relationships between soil inputs (e.g., soil amendments, pH, carbon, nitrogen and hydrogen contents, electrical conductivity, and dissolved organic carbon) and design outputs (e.g., BCFs and TFs) beforehand and because of the high accuracy of the obtained models. The controlled use of associated microorganisms to increase the efficiency of phytoremediation of HM, mainly using combinations of Brassica and Salix spp. and rhizobacteria at contaminated soils, is a promising possibility. A crucial future challenge for the expansion of their use will be to develop well-defined cost- and time-efficient tools for a credible prediction of their effectiveness on contaminated field sites.
Comparative transcript profiling reveals the mechanism of female sterility associated with seedless Ponkan mandarin (Citrus reticulata Blanco)
Authors: Xiao Jinping , Zhang Lanlan , Fan Fangjuan , Liu Xubo
Published: June 2018

Seedlessness is a highly desirable trait in citrus varieties. Sterility is the key determination for seedlessness formation. However, the molecular basis for female sterility in seedless mandarin remains unclear. Thus, a seedless Ponkan mandarin (Citrus reticulata Blanco ‘Lipeng No.2’), considered the bud mutation of normal seedy Ponkan, was collected to identify candidate genes involved in seedless variation. Suppression subtractive hybridization (SSH) screened 1091 uniESTs related to seedy and seedless Ponkan (727 singlets and 364 contigs), which mainly governed catalytic activity, transferase activity, and oxygen binding. By using RNA-Seq technology, 106 differentially expressed genes (DEGs) were captured, of which 74 were up-regulated and 32 were down-regulated. Gene Ontology and pathway analysis showed that six DEGs were enriched in the biosynthesis of secondary metabolite, whereas five DEGs were enriched in the signaling of plant hormones. The combined results of SSH and RNA-Seq indicated the importance of amino acid metabolism in seedless Ponkan. Our findings revealed that the mechanism of seedless Ponkan generation may be related to gene regulation, signal cascade, and hormone levels. This study provided a solid foundation for functional gene identification in seedless Ponkan and a good reference for relevant research on molecular mechanisms of female sterility in Ponkan mandarin.
Reachability Problems for One-Dimensional Piecewise Affine Maps
Authors: Bournez Olivier , Kurganskyy Oleksiy , Potapov Igor
Published: June 2018

Piecewise affine maps (PAMs) are frequently used as a reference model to discuss the frontier between known and open questions about the decidability for reachability questions. In particular, the reachability problem for one-dimensional PAM is still an open problem, even if restricted to only two intervals. As the main contribution of this paper we introduce new techniques for solving reachability problems based on [Formula: see text]-adic norms and weights as well as showing decidability for two classes of maps. Then we show the connections between topological properties for PAM’s orbits, reachability problems and representation of numbers in a rational base system. Finally we construct an example where the distribution properties of well studied sequences can be significantly disrupted by taking fractional parts after regular shifts. The study of such sequences could help with understanding similar sequences generated in PAMs or in well known Mahler’s [Formula: see text] problem.
Systematic study of the nature of gamma bands in A = 100–200 mass nuclei
Authors: Karday Monica , Mittal H. M. , Mehra Rohit
Published: June 2018

The [Formula: see text]-bands are analyzed through the variation of the energy of the [Formula: see text] excitation and the energies of excited level sequence of [Formula: see text]-bands with respect to various parameters. The shape phase transition observed at N = 88–90 is reviewed through its influence on the energies of [Formula: see text]-band. The correlation of the [Formula: see text] excitation energies with the collective shape signature observable [Formula: see text] indicates a connection with the nuclear equilibrium structure. The study of excited level sequence in the [Formula: see text]-band with respect to the ground band signifies that the two bands differ in deformation.
Weakly nonlinear analysis for car-following model with consideration of cooperation and time delays
Authors: Chen Dong , Sun Dihua , Zhao Min , He Yuchu , Liu Hui
Published: June 2018

In traffic systems, cooperative driving has attracted the researchers’ attention. A lot of works attempt to understand the effects of cooperative driving behavior and/or time delays on traffic flow dynamics for specific traffic flow models. This paper is a new attempt to investigate analyses of linear stability and weak nonlinearity for the general car-following model with consideration of cooperation and time delays. We derive linear stability condition and study how the combinations of cooperation and time delays affect the stability of traffic flow. Burgers’ equation and Korteweg de Vries’ (KdV) equation for car-following model considering cooperation and time delays are derived. Their solitary wave solutions and constraint conditions are concluded. We investigate the property of cooperative optimal velocity (OV) model which estimates the combinations of cooperation and time delays about the evolution of traffic waves using both analytic and numerical methods. The results indicate that delays and cooperation are model-dependent, and cooperative behavior could inhibit the stabilization of traffic flow. Moreover, delays of sensing relative motion are easy to trigger the traffic waves; delays of sensing host vehicle are beneficial to relieve the instability effect to a certain extent.
Effects of properties of silt particles on cavitating flow characteristics in a nozzle
Authors: Qiang Yan
Published: June 2018

To research the effects of properties of silt particles on cavitating flow, silt-laden cavitation flow in one 3D nozzle is simulated. Silt mean diameters are 0.005 mm, 0.007 mm, 0.009 mm, 0.010 mm, 0.012 mm, 0.013 mm, 0.015 mm, 0.020 mm, 0.026 mm, 0.030 mm, 0.035 mm, 0.040 mm, 0.046 mm, 0.050 mm and 0.056 mm. Silt concentrations vary from 1.0% to 10%. To measure the effects of silt particles, vapor contents under pure water cavitation flow and silt-laden cavitation flow conditions are calculated and compared. Results show that silt particles first promote the development of cavitation then inhibit the evolution of cavitation with the increase of silt concentration. Silt particles promotion scope decreases gradually and inhibition span increases constantly with the increase of silt mean diameter. Cavitation nuclei, vortices, slip velocity, virtual mass force and Saffman lift force have a closed relation with the promotion of silt particles. Vortices, viscosity and silt abrasion deeply influence the inhibition of cavitation.
A Proactive Decision Support System for Online Event Streams
Authors: Wang Yongheng , Zhang Xiaozan , Wang Zengwang
Published: June 2018

In-stream big data processing is an important part of big data processing. Proactive decision support systems can predict future system states and execute some actions to avoid unwanted states. In this paper, we propose a proactive decision support system for online event streams. Based on Complex Event Processing (CEP) technology, this method uses structure varying dynamic Bayesian network to predict future events and system states. Different Bayesian network structures are learned and used according to different event context. A networked distributed Markov decision processes model with predicting states is proposed as sequential decision making model. A Q-learning method is investigated for this model to find optimal joint policy. The experimental evaluations show that this method works well for congestion control in transportation system.
The stability of closed linear Weingarten spacelike hypersurfaces in foliated spacetimes
Authors: Han Hyelim
Published: June 2018

This paper discusses the stability concerning closed linear Weingarten spacelike hypersurfaces [Formula: see text] immersed in foliated spacetimes. Firstly, we show that a totally umbilic [Formula: see text] is strongly stable. Secondly, given a generalized Robertson–Walker spacetime [Formula: see text] whose warping function [Formula: see text] is under a suitable restriction, we prove that if [Formula: see text] is strongly stable, then it is totally umbilic.
pH-Dependent chromogenic properties of an orthogonal metal-C (aryl) bonded azobenzene-rhodium(III) porphyrin conjugate
Authors: Yao Shengxin , Yan Yu , Wong Ka Lai , Chan Kin Shing , Shen Zhen
Published: June 2018

An orthogonally arranged conjugate comprised of two rhodium(III) tetrakis-4-tolyporphyrins linked with an azobenzene moiety through a covalent Rh-C (aryl) bond has been facilely synthesized and characterized. Although photochemical isomerization of the azobenzene component was not observed, addition of trifluoroacetic acid (TFA) to the conjugate in a toluene solution causes significant colorimetric changes. UV-vis absorption, resonance light scattering (RLS), [Formula: see text]H-NMR and IM-MS spectra were employed to investigate the pH-dependent chromogenic behavior of the triad, which gives a new pathway for construction of pH-dependent assemblies of porphyrin-azobenzene complexes.
Generalized hybrid operators preserving exponential functions
Authors: Agrawal Deepika , Gupta Vijay
Published: June 2018

The present paper deals with the approximation properties of generalization of Lupaş–Păltănea’s operators preserving exponential functions. We obtain moments using the concept of moment generating functions and establish a Voronovskaya type theorem, uniform convergence estimate and also an asymptotic formula in quantitative sense. In the end we present comparative study through graphical representation and propose an open problem.
The Swarm Telescope Concept
Authors: Dowell Jayce , Taylor Greg B.
Published: June 2018

As telescope facilities become increasingly more capable, they also become increasingly complex and require additional resources to operate. This is particularly true for the current and future generations of “software defined telescopes” that can support a variety of observing programs simultaneously, either through commensal observations or through support for multiple pointing centers as in the case of dipole arrays or dishes equipped with phased array feeds. At the same time, many current and future facilities are also distributed over large geographic areas, making monitoring and maintenance more difficult and costly. For these reasons, we have developed a new paradigm for telescope operations called the “swarm telescope” that breaks large, single facilities into smaller groups of independent systems that can collaboratively work together to function as a single facility but with much less operational overhead. In this paper, we outline the swarm telescope concept and an example of its implementation at the Long Wavelength Array. We also discuss potential advantages of using this approach for other facilities, in particular the Next Generation Very Large Array.
Tri-culture system for pro-hapten sensitizer identification and potency classification
Authors: Lee Serom , Greenstein Talia , Shi Lingting , Maguire Tim , Schloss Rene , Yarmush Martin
Published: June 2018

Allergic contact dermatitis (ACD) is an inflammatory disease that impacts 15–20% of the general population and accurate screening methods for chemical risk assessment are needed. However, most approaches poorly predict pre- and pro-hapten sensitizers, which require abiotic or metabolic conversion prior to inducing sensitization. We developed a tri-culture system comprised of MUTZ-3-derived Langerhans cells, HaCaT keratinocytes, and primary dermal fibroblasts to mimic the cellular and metabolic environments of skin sensitization. A panel of non-sensitizers and sensitizers was tested and the secretome was evaluated. A support vector machine (SVM) was used to identify the most predictive sensitization signature and classification trees identified statistical thresholds to predict sensitizer potency. The SVM computed 91% tri-culture prediction accuracy using the top 3 ranking biomarkers (IL-8, MIP-1 [Formula: see text], and GM-CSF) and improved the detection of pre- and pro-haptens. This in vitro assay combined with in silico data analysis presents a promising approach and offers the possibility of multi-metric analysis for enhanced ACD sensitizer screening.
Hybrid turbidite–contourite systems of the Tanzanian margin
Authors: Sansom Pamela
Published: June 2018

Extensive 3D seismic datasets acquired during exploration offshore southern Tanzania have revealed the complex architecture of two contrasting styles of hybrid turbidite–contourite deposits that formed in the Cretaceous (Albian–Early Campanian) and Paleogene (Paleocene–Oligocene). Both sequences are characterized by migrating channel-levee complexes, interpreted to record, and be diagnostic of, the synchronous interaction of eastward, downslope flowing turbidity currents and northerly, along-slope flowing contour currents. Flow stripping of the fine-grained suspended part of the turbulent flow by weak contour currents led to the formation of expanded levee-drifts on the northern (downstream) side of the channels, which prograded southwards (upstream), driving southwards migration of the turbidite channel axis.

The difference in the architecture of the two successions is due to the variation in slope topography at the time turbidite activity commenced and the frequency of coarse clastic input into the basin. Cretaceous (Albian–Campanian) turbidite systems were strongly controlled by the position of pre-existing contourite drifts and moats. The contorted geometry of the system provided loci for the deposition of Cretaceous reservoirs comprising thick, amalgamated channel deposits with a high net-to-gross ratio (N:G) and good vertical connectivity, and intra-slope fans with lower N:G and poor vertical connectivity.

Paleogene turbidite channels initially evolved on a smooth slope. Sustained southward channel migration produced Paleogene reservoirs comprising complexly laterally-connected sheets of channel and lobe deposits above a southward-younging, diachronous compound unconformity. In both hybrid systems, contour current influence modified the geometry of the turbidite systems, resulting in temporal and spatial partitioning of the depocentres on the slope.
FEMOSAA
Authors: Chen Tao , Li Ke , Bahsoon Rami , Yao Xin
Published: June 2018

Self-Adaptive Software (SAS) can reconfigure itself to adapt to the changing environment at runtime, aiming to continually optimize conflicted nonfunctional objectives (e.g., response time, energy consumption, throughput, cost, etc.). In this article, we present Feature-guided and knEe-driven Multi-Objective optimization for Self-Adaptive softwAre (FEMOSAA), a novel framework that automatically synergizes the feature model and Multi-Objective Evolutionary Algorithm (MOEA) to optimize SAS at runtime. FEMOSAA operates in two phases: at design time, FEMOSAA automatically transposes the engineers’ design of SAS, expressed as a feature model, to fit the MOEA, creating new chromosome representation and reproduction operators. At runtime, FEMOSAA utilizes the feature model as domain knowledge to guide the search and further extend the MOEA, providing a larger chance for finding better solutions. In addition, we have designed a new method to search for the knee solutions, which can achieve a balanced tradeoff. We comprehensively evaluated FEMOSAA on two running SAS: One is a highly complex SAS with various adaptable real-world software under the realistic workload trace; another is a service-oriented SAS that can be dynamically composed from services. In particular, we compared the effectiveness and overhead of FEMOSAA against four of its variants and three other search-based frameworks for SAS under various scenarios, including three commonly applied MOEAs, two workload patterns, and diverse conflicting quality objectives. The results reveal the effectiveness of FEMOSAA and its superiority over the others with high statistical significance and nontrivial effect sizes.
Fitness Penalties in the Evolution of Fungicide Resistance
Authors: Hawkins N.J. , Fraaije B.A.
Published: June 2018

The evolution of resistance poses an ongoing threat to crop protection. Fungicide resistance provides a selective advantage under fungicide selection, but resistance-conferring mutations may also result in fitness penalties, resulting in an evolutionary trade-off. These penalties may result from the functional constraints of an evolving target site or from the resource allocation costs of overexpression or active transport. The extent to which such fitness penalties are present has important implications for resistance management strategies, determining whether resistance persists or declines between treatments, and for resistance risk assessments for new modes of action. Experimental results have proven variable, depending on factors such as temperature, nutrient status, osmotic or oxidative stress, and pathogen life-cycle stage. Functional genetics tools allow pathogen genetic background to be controlled, but this in turn raises the question of epistatic interactions. Combining fitness penalties under various conditions into a field-realistic scenario poses an important future challenge.
Voltage-gated Ca2+channel activity modulates smooth muscle cell calcium waves in hamster cremaster arterioles
Authors: Jackson William F. , Boerman Erika M.
Published: June 2018

Cremaster muscle arteriolar smooth muscle cells (SMCs) display inositol 1,4,5-trisphosphate receptor-dependent Ca2+waves that contribute to global myoplasmic Ca2+concentration and myogenic tone. However, the contribution made by voltage-gated Ca2+channels (VGCCs) to arteriolar SMC Ca2+waves is unknown. We tested the hypothesis that VGCC activity modulates SMC Ca2+waves in pressurized (80 cmH2O/59 mmHg, 34°C) hamster cremaster muscle arterioles loaded with Fluo-4 and imaged by confocal microscopy. Removal of extracellular Ca2+dilated arterioles (32 ± 3 to 45 ± 3 μm, n = 15, P < 0.05) and inhibited the occurrence, amplitude, and frequency of Ca2+waves ( n = 15, P < 0.05), indicating dependence of Ca2+waves on Ca2+influx. Blockade of VGCCs with nifedipine (1 μM) or diltiazem (10 μM) or deactivation of VGCCs by hyperpolarization of smooth muscle with the K+channel agonist cromakalim (10 μM) produced similar inhibition of Ca2+waves ( P < 0.05). Conversely, depolarization of SMCs with the K+channel blocker tetraethylammonium (1 mM) constricted arterioles from 26 ± 3 to 14 ± 2 μm ( n = 11, P < 0.05) and increased wave occurrence (9 ± 3 to 16 ± 3 waves/SMC), amplitude (1.6 ± 0.07 to 1.9 ± 0.1), and frequency (0.5 ± 0.1 to 0.9 ± 0.2 Hz, n = 10, P < 0.05), effects that were blocked by nifedipine (1 μM, P < 0.05). Similarly, the VGCC agonist Bay K8644 (5 nM) constricted arterioles from 14 ± 1 to 8 ± 1 μm and increased wave occurrence (3 ± 1 to 10 ± 1 waves/SMC) and frequency (0.2 ± 0.1 to 0.6 ± 0.1 Hz, n = 6, P < 0.05), effects that were unaltered by ryanodine (50 μM, n = 6, P > 0.05). These data support the hypothesis that Ca2+waves in arteriolar SMCs depend, in part, on the activity of VGCCs.

NEW & NOTEWORTHY Arterioles that control blood flow to and within skeletal muscle depend on Ca2+influx through voltage-gated Ca2+channels and release of Ca2+from internal stores through inositol 1,4,5-trisphosphate receptors in the form of Ca2+waves to maintain pressure-induced smooth muscle tone.
Inhibition of programmed necrosis limits infarct size through altered mitochondrial and immune responses in the aged female rat heart
Authors: Garvin Alexandra M. , Jackson Morgan A. , Korzick Donna H.
Published: June 2018

Both advancing age and estrogen loss exacerbate acute myocardial infarction in the female heart. However, the mechanistic underpinnings of age-related differences in cell death after ischemia-reperfusion (I/R) injury in female subjects and reductions in cardioprotective reserve capacity remain largely unexplored. The aim of the present study was to determine the efficacy of programmed necrosis inhibition on infarct size reduction and preservation of left ventricular (LV) function after I/R injury with female aging. Fischer 344 rats were ovariectomized (OVX) at 15 mo and studied at 24 mo (MO OVX) versus adult rats with intact ovaries (6 mo). After in vivo coronary artery ligation (55-min ischemia and 2- or 6-h reperfusion), necrostatin-1 (Nec-1; 3.5 or 5.7 mg/kg) delivered upon reperfusion significantly reduced infarct size by 37% and improved LV function in the MO OVX group ( P < 0.01). Although age-associated elevations in cyclophilin D and mitochondrial acetylation ( P < 0.001) were unaffected by Nec-1, profound reductions in IL-1, IL-6, and TNF-α ( P < 0.05) as well as cardiac immune cell infiltration were observed in MO OVX but not adult rats. We conclude that chronic inflammation and postmenopausal estrogen deficiency conspire to exacerbate acute infarction through a mechanism involving exaggerated mitochondria-mediated programmed necrosis through receptor-interacting protein 1 signaling. Modulatory effects of programmed necrosis inhibition on proinflammatory cytokine production after I/R reveal a potentially important mechanistic target to restore and preserve cardiac function in the OVX aged female heart.

NEW & NOTEWORTHY Myocardial infarct size reduction by inhibition of programmed necrosis in aged female subjects suggests a dominant cell death pathway. Alterations in mitochondrial protein levels and acetylation underscore a mitochondria-dependent mechanism, whereas the profound cytokine reduction in aged subjects alone points to a divergent role for immune modulation of programmed necrosis and viable therapeutic target.
Influenza virus infection modulates the death receptor pathway during early stages of infection in human bronchial epithelial cells
Authors: Othumpangat Sreekumar , Beezhold Donald H. , Noti John D.
Published: June 2018

Host-viral interaction occurring throughout the infection process between the influenza A virus (IAV) and bronchial cells determines the success of infection. Our previous studies showed that the apoptotic pathway triggered by the host cells was repressed by IAV facilitating prolonged survival of infected cells. A detailed understanding on the role of IAV in altering the cell death pathway during early-stage infection of human bronchial epithelial cells (HBEpCs) is still unclear. We investigated the gene expression profiles of IAV-infected vs. mock-infected cells at the early stage of infection with a PCR array for death receptor (DR) pathway. At early stages infection (2 h) with IAV significantly upregulated DR pathway genes in HBEpCs, whereas 6 h exposure to IAV resulted in downregulation of the same genes. IAV replication in HBEpCs decreased the levels of DR pathway genes including TNF-receptor superfamily 1, Fas-associated death domain, caspase-8, and caspase-3 by 6 h, resulting in increased survival of cells. The apoptotic cell population decreased in 6 h compared with the 2 h exposure to IAV. The PCR array data were imported into Ingenuity Pathway Analysis software, resulting in confirmation of the model showing significant modulation of the DR pathway. Our data indicate that a significant transcriptional regulation of apoptotic, necrotic, and DR genes occur at early and late hours of infection that are vital in modulating the survival of host cells and replication of IAV. These data may have provided a likely roadmap for translational approaches targeting the DR pathway to enhance apoptosis and inhibit replication of the virus.
Skeletal Muscle Loss Is an Imaging Biomarker of Outcome after Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer
Authors: Lee Jie , Chang Chih-Long , Lin Jhen-Bin , Wu Meng-Hao , Sun Fang-Ju , Jan Ya-Ting , Hsu Shih-Ming , Chen Yu-Jen
Published: June 2018

Purpose: This study investigates the association between body composition change during concurrent chemoradiotherapy (CCRT) and outcome in patients with locally advanced cervical cancer (LACC).

Experimental Design: Pre- and posttreatment CT images of 245 patients with LACC who were treated between 2004 and 2015 were analyzed. Skeletal muscle index (SMI) and density (SMD), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured from two sets of CT images at the level of the L3 vertebra. Sarcopenia and a low SMD were defined using published cut-off points. Predictors of overall survival (OS) and cancer-specific survival (CSS) were analyzed using Cox regression models.

Results: The median follow-up was 62.7 (range, 7.3–152.3) months. Among the 245 patients, 127 (51.8%) had pretreatment sarcopenia, and 154 (62.9%) had a low SMD. SMI did not decrease significantly during CCRT, 0.6%/150 days [95% confidence interval (CI), −1.8–0.6; P = 0.35]. However, SMI loss during CCRT of >10.0%/150 days was independently associated with poorer OS (HR, 6.02; 95% CI, 3.04–11.93; P < 0.001) and CSS (HR, 3.49; 95% CI, 1.44–8.42; P = 0.006) when adjusted for FIGO stage, pathology, and treatment. Pretreatment sarcopenia and change of SMD, SATI, and VATI during CCRT were not associated with survival.

Conclusions: Skeletal muscle measurements could be imaging biomarkers to predict outcomes for patients with LACC in clinical practice. Further studies are needed to determine whether multimodal interventions can preserve skeletal muscle mass and thereby improve survival. Clin Cancer Res; 24(20); 5028–36. ©2018 AACR.
Dual Targeting of ERBB2/ERBB3 for the Treatment of SLC3A2-NRG1–Mediated Lung Cancer
Authors: Shin Dong Hoon , Jo Jeong Yeon , Han Ji-Youn
Published: June 2018

We characterized the SLC3A2-NRG1 fusion gene in non–small cell lung cancer (NSCLC) and established an effective therapy for patients with SLC3A2-NRG1 fusion–positive cancer. The SLC3A2-NRG1 fusion product was composed of the SLC3A2 transmembrane domain and the EGF-like domain of the neuregulin 1 (NRG1) protein. The NRG1 family is classified as a ligand of the ERBB family. We identified ERBB3 and ERBB4 in the ERBB family as binding partners of the SLC3A2-NRG1 fusion protein via ligand and receptor binding assays. We confirmed that SLC3A2-NRG1 increased formation of a heterocomplex of ERBB3 with ERBB2. Activation of the ERBB2–ERBB3 heterocomplex by SLC3A2-NRG1 increased colony formation and tumor growth through PI3K-AKT and MAP kinase. The specific siRNAs for ERBB2 and ERBB3, pertuzumab, lumretuzumab, and afatinib all decreased ERBB2–ERBB3 heterocomplex formation, phosphorylation of each protein, and their downstream signaling. In addition, single treatment with pertuzumab, lumretuzumab, or afatinib decreased tumor volume and weight, whereas combination treatment with these drugs and taxol enhanced generation of cleaved caspase 3, PARP, and TUNEL-positive cells compared with each single treatment. Thus, the SLC3A2-NRG1 fusion gene plays an important role in lung cancer cell proliferation and tumor growth by promoting generation of the ERBB2–ERBB3 heterocomplex, its phosphorylation, and activation of the PI3K/ERK/mTOR signaling pathway. Inhibition of either ERBB2 or ERBB3 alone did not completely shut down downstream signaling of ERBB2 and ERBB3; however, inhibition of both ERBB2 and ERBB3 blocked downstream signaling activated by SLC3A2-NRG1 fusion. ERBB2 and ERBB3 might be promising targets for treatment of SLC3A2-NRG1–positive tumors. Mol Cancer Ther; 17(9); 2024–33. ©2018 AACR.
SALTO - Study Protocol and Rationale of a Community-Oriented Obesity Prevention Program in the Kindergarten
Authors: Ring-Dimitriou Susanne , Freudenthaler Thomas , Aistleitner Verena , Horvath Gertrude , Stallinger Julia , Dimitriou Minas , Ardelt-Gattinger Elisabeth , Weghuber Daniel
Published: June 2018

Background: The prevalence of early childhood overweight and obesity in Austria has reached average European levels of 20% in boys and 18% in girls. The rationale and study protocol of SALTO, Salzburg Together against Obesity will be presented, which is aimed to assist adults in increasing the rate of 4- to 6-year-old children with a healthy body weight. Methods: A controlled longitudinal sequential study design consisting of 14 intervention (IK) and 8 control (CK) kindergarten was used to investigate the effect of actions tailored for teachers and parents on BMI among 4- to 6-year-old children. The study launched in November 2014 was approved by the ethics committee of the University of Salzburg. Results: 681 children, 181 parents (119 mothers, 62 fathers) and 30 teachers were investigated until October 2016. Preliminary analyses revealed that more boys (19%) and fathers (60% IK, 43% CK) were overweight and obese than girls (16%) and mothers (19% IK, 20% CK). Conclusion: The challenges faced by the SALTO staff in the implementation of health-promoting actions in the kindergarten are manifold. The Community-Oriented Core Setting (COCS) intervention approach will show whether the actions will reduce the percentage of obesity and be sustainable in the long term.
Chronic Intestinal Pseudo-Obstruction in Systemic Sclerosis: An Uncommon Presentation
Authors: Shah Jamil , Shahidullah Abul
Published: June 2018

Chronic intestinal pseudo-obstruction (CIPO) is an uncommon disorder characterized by the presence of bowel dilatation and abnormal motility. It is an important cause of chronic intestinal failure in patients with systemic sclerosis (SSc). Although intestinal pseudo-obstruction is an infrequent reason for hospitalization in these patients, it has been correlated with high in-hospital mortality compared to SSc patients hospitalized for other reasons as well as patients with intestinal pseudo-obstruction arising from other causes. Patients present with signs and symptoms of mechanical bowel obstruction, such as nausea, vomiting, constipation, abdominal pain, and abdominal distension, in the absence of an anatomic lesion blocking the movement of intestinal contents. Despite breakthroughs in our understanding of this disorder, these patients continue to be treated largely with organ-based symptomatic therapy. Unfortunately, despite treatment, they often experience decreased quality of life and impairment in their everyday lives. Here, we present an interesting case of an individual with SSc for many years who presented with signs and symptoms of CIPO.
Christianity: “A Manner of Dividing the Sensible”
Authors: Gow Andrew
Published: June 2018

Anidjar’s Blood can be read, with Amy Hollywood, as a political intervention designed to alienate and creatively reuse the familiar terms ‘blood’ and ‘Christianity’ to mean quite different things, namely a set of biologically, emotionally, and politically charged metaphors circulating within and fuelling a hegemonic cultural world system. While this is a clear possible reading throughout, Anidjar provides an explicit key to justify these meanings only on page 258, allowing that he has used each term as ‘catachresis’— to command our attention but also to redirect it. Contrary to Francis Landy’s wish that Andijar provide an accounting of how (actual) blood in (actual) Christian tradition relates to blood in Judaism, I suggest that Anidjar’s project requires nothing of the sort, working as it does at an entire level of abstraction above the plane of paratactically organized and comparable ‘religions’.
Do High-Achieving Students Benefit From Honors College Participation? A Look at Student Engagement for First-Year Students and Seniors
Authors: Miller Angie L. , Dumford Amber D.
Published: June 2018

This study investigates findings from the National Survey of Student Engagement (NSSE), comparing various aspects of student engagement between honors college and general education students. Responses from 1,339 honors college students and 7,191 general education students across 15 different universities suggest a positive impact for honors college participation on reflective and integrative learning, use of learning strategies, collaborative learning, diverse discussions, student–faculty interaction, and quality of interactions for first-year students, even when controlling for student and institutional characteristics. For senior students, honors college participation was related to more frequent student–faculty interaction. Potential experiential and curricular reasons for these differences are discussed, along with implications for educators, researchers, parents, and students.
Family Socialization for Racism and Heterosexism: Experiences of Latinx Sexual Minority Adolescents and Young Adults
Authors: Toomey Russell B. , Shramko Maura , Flores Melissa , Anhalt Karla
Published: June 2018

Experiences of racism and heterosexism are common among marginalized adolescents and young adults. Family socialization processes that aim to prepare young people for bias have been studied among racial–ethnic minority populations; however, they have not been investigated among sexual minority populations. This study examined the associations among preparation for bias related to ethnicity and sexual orientation, minority stressors (i.e., bias-based victimization and discrimination) attributed to ethnicity and sexual orientation, and well-being (i.e., depressive symptoms and self-esteem) in a sample of 236 Latinx adolescents and young adults ( Mage = 19). All minority stressors were associated with poorer well-being. Preparation for bias related to ethnicity was not associated with well-being; however, preparation for bias related to sexual orientation was associated with lower self-esteem. Furthermore, preparation for bias related to sexual orientation moderated the association between bias-based victimization and depressive symptoms such that the association was only significant at high levels of preparation.