bluuebunny/crossref_metadata_2025 huggingface dataset:
Navigating the ‘broad freeway’: ocean currents and inland isolation drive diversification in the Pandanus tectorius complex (Pandanaceae)
Authors: Gallaher Timothy , Callmander Martin W. , Buerki Sven , Setsuko Suzuki , Keeley Sterling C.
Published: December 2016

Aim

To test for and describe the genetic structure of the Pandanus tectorius complex, a group of closely related ocean‐dispersed plants and members of the Indo‐Pacific coastal strand community.

Location

Tropical Indo‐Pacific (coastal East Africa to Polynesia).

Methods

We sampled 535 individuals (46 localities) from throughout the range of the complex. Fifteen microsatellite loci were used to detect and characterize population structure and estimate migration rates between island groups and broad regions.

Results

Hierarchical population structure was detected. Samples group into an eastern cluster (Hawaii and coastal South‐Central Pacific localities) and a western cluster [Western Pacific (WP) through Indian Ocean]. Within these two clusters, at least six regional subclusters were detected including samples from the Indian Ocean + South China Sea (SCS), Ogasawara Islands, WP, inland South‐Central Pacific, coastal South‐Central Pacific and Hawaii. Migration rates between regions are low leading to isolation and genetic differentiation while within regions, rates are much higher. In most cases, inland populations are genetically differentiated from nearby coastal counterparts.

Main conclusions

Substantial population structure occurs across the range of the P. tectorius complex due to dispersal limitation across stretches of open ocean and patterns of ocean currents. Low levels of asymmetric westward migration, consistent with the direction of ocean currents in the Pacific, links Hawaii and the South‐Central Pacific with populations further to the west preventing complete isolation. SCS + Indian Ocean populations are distinct from those in the Pacific due to limited dispersal between these regions. The isolation of inland populations on several islands also contributes to genetic differentiation. While population clusters have a clear geographical basis they are not completely congruent with previously recognized taxa.
Oral Hygiene in the Elderly with Different Degrees of Cognitive Impairment and Dementia
Authors: Gil‐Montoya José Antonio , Sánchez‐Lara Inés , Carnero‐Pardo Cristobal , Fornieles‐Rubio Francisco , Montes Juan , Barrios Rocío , Gonzalez‐Moles Miguel Angel , Bravo Manuel
Published: December 2016

The control of bacterial dental plaque through daily oral hygiene is essential to prevent oral diseases such as caries or periodontal disease, especially in at‐risk populations, including the elderly with mild cognitive impairment and dementia. The aim of this study was to determine the association between different levels of cognitive impairment and dementia in an elderly population and their capacity to maintain adequate oral hygiene. A case–control study (elderly with versus without mild cognitive impairment or dementia) was performed in Granada, Spain. Outcome variables were tooth/prosthesis‐brushing frequency/day, bacterial plaque index, and gingival bleeding index. Statistical models were adjusted by age, sex, educational level, and tobacco and alcohol habits. The study included 240 cases and 324 controls. The final model, adjusted by age, sex, educational level, and tobacco and alcohol consumption, showed a significant association between degree of cognitive impairment and daily oral hygiene, accumulation of bacterial plaque, and gingival bleeding. In summary, deficient daily oral hygiene, evidenced by greater bacterial dental plaque accumulation and gingival inflammation, is independently associated with cognitive impairment, even at its earliest stage.
Agreement and Predictive Validity Using Less‐Conservative Foundation for the National Institutes of Health Sarcopenia Project Weakness Cutpoints
Authors: Chiles Shaffer Nancy , Ferrucci Luigi , Shardell Michelle , Simonsick Eleanor M. , Studenski Stephanie
Published: December 2016

Objectives

To derive lean mass cutpoints based on a less‐conservative Foundation for the National Institutes of Health (FNIH) Sarcopenia Project Weakness cutpoint for grip strength (WeakI) and to assess their agreement with European Working Group on Sarcopenia in Older People (EWGSOP) and prediction of incident slow walking and mortality.

Design

Longitudinal analysis.

Setting

Baltimore Longitudinal Study of Aging.

Participants

Individuals aged 65 and older (287 men, 258 women) with 2 to 10 years of follow‐up.

Measurements

Weakness was determined according to handgrip strength using a hand dynamometer, appendicular lean mass (ALM) using dual‐energy X‐ray absorptiometry, and walking speed according to 6‐m usual pace walk speed. Analyses were performed using classification and regression tree analysis, Cohen's kappa, and Cox models.

Results

Cutpoints derived from WeakI for ALM (ALMI) were less than 21.4 kg in men and less than 14.1 kg in women and for ALM adjusted for body mass index (ALM/BMII) were less than 0.725 in men and less than 0.591 in women. Kappas with EWGSOP were 0.65 for men and 0.75 for women for ALMI and 0.34 for men and 0.47 for women for ALM/BMII. Men with WeakI + ALMI were twice as likely to develop slow walking as those not weak with normal ALMI (Hazard ratio (HR) = 2.44, 95% confidence interval (CI) = 1.02‐5.82). Under EWGSOP, men with weakness and low RALM were almost 3 times as likely to develop slow walking as those not weak with normal RALM (HR = 2.91, 95% CI = 1.11‐7.62). Neither approach predicted incident slow walking in women.

Conclusion

The ALMI cutpoints agree with EWGSOP and predict slow walking in men. Future studies should explore sex differences in the relationship between body composition and physical function and the effect of change in muscle mass on muscle strength and physical function.
The Moral Economy of Money between the Gold Standard and the New Deal
Authors: Feinig Jakob
Published: December 2016

In this article, I show that Depression‐era popular opposition to gold standard orthodoxy had an identifiable impact on New Deal policy. Popular pressure was rooted in a political‐economic vision I call the “moral economy of money.” The moral economy of money included a critique of the gold standard and creditor classes and advocated a democratization of control over money and credit to restore social justice. Against many odds, Roosevelt narrowly defeated congressional majorities connected to popular groups bent on mandating Treasury currency issue. At the same time, he pioneered a discourse that became generalized in the following decades and discouraged a reemergence of the moral economy of money.
Factors associated with oral health‐related quality of life among safety‐net clinic patients
Authors: Kamimura Akiko , Gull Bethany , Weaver Shannon , Wright Lindsey , Edwards Alysa , Nourian Kimiya , Ashby Jeanie , Erickson Lea E.
Published: December 2016

Objectives

Oral health‐related quality of life (OHRQoL) is an important health indicator not only for individuals but also for oral health care providers to treat a person holistically. Previous studies focused on OHRQoL do not provide comprehensive knowledge regarding low‐income patients in the United States, many of whom have chronic health conditions that can affect their oral health. The purpose of this study is to examine factors associated with OHRQoL among low‐income, uninsured patients of safety‐net providers, which provide free or reduced fee medical and/or dental care to underserved populations.

Methods

Uninsured patients (N = 584) participated in a self‐administered survey in May and June 2016 at a safety‐net clinic in the United States serving a low‐income uninsured population, which provides limited oral health care services. This study used cross‐sectional design and a nonprobability sample. The dependent variable was OHRQoL measured using the Oral Health Impact Profile‐14. Chi square tests, Analysis of Variance tests, and multiple regression were used for statistical analysis.

Results

Higher levels of dental care neglect and lower frequency of oral hygiene practice were associated with lower levels of OHRQoL (P < 0.01). Participants utilizing a diabetes clinic reported better OHRQoL than those who were not patients of a diabetes clinic (P < 0.05). US born English speakers had worse general health and OHRQoL compared to non‐US born English speakers and Spanish speakers (P < 0.01).

Conclusions

An intervention to remedy dental neglect is recommended to improve OHRQoL among uninsured safety‐net patients.
Effect of the Presence of a Mobile Phone during a Spatial Visual Search
Authors: Ito Motohiro , Kawahara Jun‐Ichiro
Published: December 2016

Recent studies suggest that the “mere presence” of a mobile phone impairs social interactions and neuropsychological test performance. The present study examined whether the presence of a mobile phone causes spatial bias toward the device during a visual search task. Participants identified a target among spatially distributed non‐targets. We manipulated three factors: device presence (mobile phone or notepad), target congruency (congruent or incongruent), and attentional load (set size 8 or 24). A mobile phone (or a notepad in the control condition) was placed on the left side of the computer screen. Participants also completed a questionnaire to measure Internet usage and attachment. Participants with high scores on the questionnaire rapidly identified the target at the congruent (same side as the phone) location, but the mere presence effect did not occur in this condition. In contrast, participants with low scores on the questionnaire demonstrated the mere presence effect, but no spatial bias was observed. These results suggest that the mere presence effect can be modulated by individual differences in the degree to which a device is appealing.
Analysis of School Enrollment in Ghana: A Sequential Approach
Authors: Iddrisu Abdul Malik , Danquah Michael , Quartey Peter
Published: December 2016

In this paper, we depart from the standard way of analyzing school enrollment by accounting explicitly for educational selectivity in order to examine the determinants of child school enrollment in Ghana. Using data from the Ghana Living Standard Survey round 6 (GLSS 6), we estimate a three‐step sequential logit model for the determinants of secondary school enrollment and its dependence on completing primary school. We find that family resources such as parental education, household income and the gender of the head of the household play a role in households' child schooling decisions. Educated parents are relatively more likely to enroll their children in primary school and keep them in school until they complete primary education. As well, we show that educated parents do not promote a gender‐biased investment in the schooling of children at the primary level. While household welfare does not influence children's entry into primary school importantly, their completion of primary school depends on household welfare. The study sheds more light on the pro‐male bias phenomenon regarding entry into primary school and primary school completion. Policies to promote the achievement of Sustainable Development Goal 4 in Ghana must be grade sensitive.
Proposed revised nomenclature for transfusion‐related acute lung injury
Authors: Toy Pearl , Kleinman Steven H. , Looney Mark R.
Published: December 2016

A decade ago, definitions of “transfusionߚrelated acute lung injury (TRALI)” and “possible TRALI” were standardized for research and clinical diagnosis. Since then, evidence has confirmed that TRALI is often due to transfusion of white blood cell antibodies to at‐risk patients, and the term “TRALI, antibody mediated” is appropriate for such cases. Other TRALI cases are non–antibody mediated. Because specific, nonantibody transfusion factors have not yet been confirmed to cause TRALI in humans, the general term “TRALI, non–antibody mediated” is appropriate for such cases. In contrast, evidence is against possible TRALI being due to transfusion with the more likely cause of the acute respiratory distress syndrome (ARDS) being the alternative ARDS risk factor present in these patients. We propose to drop the misleading term “possible TRALI” and to rename this category of cases as “transfused ARDS.” These nomenclature updates will more accurately categorize ARDS cases that develop after transfusion.
HLA‐DRB3*01:01 is a predictor of immunization against human platelet antigen‐1a but not of the severity of fetal and neonatal alloimmune thrombocytopenia
Authors: Wienzek‐Lischka Sandra , König Inke R. , Papenkort Eva‐Maria , Hackstein Holger , Santoso Sentot , Sachs Ulrich J. , Bein Gregor
Published: December 2016

BACKGROUND

Most cases of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are caused by maternal alloantibodies against human platelet antigen‐1a (HPA‐1a). Alloimmunization mainly occurs in HPA‐1a–negative mothers who are carriers of the HLA‐DRB3*01:01 allele. Recently, it has been reported that the combined presence of HLA‐DRB3*01:01 and HLA‐DRB4*01:01P was associated with severity of FNAIT. We tested this hypothesis by analyzing a large cohort of cases and controls.

STUDY DESIGN AND METHODS

In total, 101 mothers with a history of FNAIT caused by anti‐HPA‐1a were investigated. HLA‐DRB1, ‐DRB3, ‐DRB4, and ‐DRB5 genotypes were determined by Luminex technology. Haplotype frequencies were compared between cases and 100 controls. The platelet (PLT) counts of neonates and the incidence of intracranial hemorrhage (ICH) were compared between subgroups defined by genotype.

RESULTS

Of the HPA‐1a–immunized mothers, 98% (99/101) carried at least one copy of HLA‐DRB3*01:01. Carriage of HLA‐DRB3*01:01 was significantly associated with immune response to HPA‐1a (odds ratio, 92.3; 95% confidence interval, 26.9‐317.1; p = 1.34 × 10−12). No association between HLA‐DRB3*01:01 and HLA‐DRB4*01:01P alone or in combination with the PLT count of the newborns or the incidence of ICH was detected.

CONCLUSION

In contrast to HLA‐DRB4*01:01P, the inheritance of HLA‐DRB3*01:01 is strongly associated with the propensity for mounting a humoral immune response against fetal HPA‐1a antigen. Neither a homozygous nor a compound heterozygous gene dose predicts the severity of the disease. Testing for the presence of HLA‐DRB3*01:01 might be very useful in counseling women at risk of FNAIT due to anti‐HPA‐1a.
Exogenous induction of unphosphorylated PTEN reduces TGFβ‐induced extracellular matrix expressions in lung fibroblasts
Authors: Kimura Motohiro , Hashimoto Naozumi , Kusunose Masaaki , Aoyama Daisuke , Sakamoto Koji , Miyazaki Shinichi , Ando Akira , Omote Norihiro , Imaizumi Kazuyoshi , Kawabe Tsutomu , Hasegawa Yoshinori
Published: December 2016

Transforming growth factor β (TGFβ) plays an important role in regulating aberrant extracellular matrix (ECM) production from alveolar/epithelial cells (AECs) and fibroblasts in pulmonary fibrosis. Although the tumor suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) can negatively control many TGFβ‐activated signaling pathways via the phosphatase activity, hyperactivation of the TGFβ‐related signaling pathways is often observed in fibrosis. Loss of PTEN expression might cause TGFβ‐induced ECM production. In addition, TGFβ was recently shown to induce loss of PTEN enzymatic activity by phosphorylating the PTEN C‐terminus. Therefore, we hypothesized that exogenous transfer of unphosphorylated PTEN (PTEN4A) might lead to reduce TGFβ‐induced ECM expression in not only epithelial cells but also fibroblasts. Adenovirus‐based exogenous PTEN4A induction successfully reduced TGFβ‐induced fibronectin expression and retained β‐catenin at the cell membrane in human epithelial cells. Exogenous unphosphorylated PTEN also attenuated TGFβ‐induced ECM production and inhibited TGFβ‐induced β‐catenin translocation in a human fibroblast cell line and in mouse primary isolated lung fibroblasts. Conversely, TGFβ‐induced α‐smooth muscle actin expression did not seem to be inhibited in these fibroblasts. Our data suggest that exogenous administration of unphosphorylated PTEN might be a promising strategy to restore TGFβ‐induced loss of PTEN activity and reduce aberrant TGFβ‐induced ECM production from epithelial cells and fibroblasts in lung fibrosis as compared with wild‐type PTEN induction.
Study on the Strategy of Social Policy Integration in the Construction of the Yangtze River Delta City Group
Authors: Bi Xingke , Yu Kai
Published: December 2016

"The development plan of Yangtze River Delta city group" puts forward to promote the construction of the Yangtze River Delta city group and speed up the optimization and upgrading of the Yangtze River Delta city group. How to achieve social policy integration is the key to the construction of the Yangtze River Delta city group. This paper analyzes the factors that hinder the social policy integration of the Yangtze River Delta city group from employment, social security, health care, education and housing security and other aspects. Then we use the welfare pluralism theory to analyze the obstacles from the government, the society and the family of three subjects, and put forward the corresponding measures to solve the problems.
Recognition of International Education in Japanese Teachers
Authors: Yoshida Masami
Published: December 2016

Education for international understanding in Japan was focused to develop its own national identity as well as to recognize its coexistence through intercultural education. Then, we have investigated the opinions of Japanese school teachers in terms of their recognition of the necessary content to introduce school instruction of intercultural education using a questionnaire method. In the questionnaire, 14 items of three principles were extracted from the criteria of UNESCO (United Nations Educational, Scientific, and Cultural Organization). For analyzing the collected data, the geometric mean was used. Subsequently, a one-way ANOVA test and multiple-comparison procedures were conducted. By including teachers in suburban areas in Japan, we obtained 123 valid responses. All items showed a necessary level of geometric means, and particularly items of the first principle “respect cultural identity” and items of the second principle “provide knowledge for participation” showed statistically significant positive necessity levels. However, an answer of “I have never thought” increased in the third principle “provide a chance to contribute” that was closely related to present world concern of global citizenship education and statistically was not significant. From the result of the multiple-comparison procedures of the second principle and the third principle, seven pairs of statistically different items were extracted. Then, we discussed the enhancement between Japan and UNESCO and influence of school environment in Japan.
On the Functional Role of Valve Interstitial Cell Stress Fibers: A Continuum Modeling Approach
Authors: Sakamoto Yusuke , Buchanan Rachel M. , Sanchez-Adams Johannah , Guilak Farshid , Sacks Michael S.
Published: December 2016

The function of the heart valve interstitial cells (VICs) is intimately connected to heart valve tissue remodeling and repair, as well as the onset and progression of valvular pathological processes. There is yet only very limited knowledge and extant models for the complex three-dimensional VIC internal stress-bearing structures, the associated cell-level biomechanical behaviors, and how they change under varying activation levels. Importantly, VICs are known to exist and function within the highly dynamic valve tissue environment, including very high physiological loading rates. Yet we have no knowledge on how these factors affect VIC function. To this end, we extended our previous VIC computational continuum mechanics model (Sakamoto, et al., 2016, “On Intrinsic Stress Fiber Contractile Forces in Semilunar Heart Valve Interstitial Cells Using a Continuum Mixture Model,” J. Mech. Behav. Biomed. Mater., 54(244–258)). to incorporate realistic stress-fiber geometries, force-length relations (Hill model for active contraction), explicit α-smooth muscle actin (α-SMA) and F-actin expression levels, and strain rate. Novel micro-indentation measurements were then performed using cytochalasin D (CytoD), variable KCl molar concentrations, both alone and with transforming growth factor β1 (TGF-β1) (which emulates certain valvular pathological processes) to explore how α-SMA and F-actin expression levels influenced stress fiber responses under quasi-static and physiological loading rates. Simulation results indicated that both F-actin and α-SMA contributed substantially to stress fiber force generation, with the highest activation state (90 mM KCL + TGF-β1) inducing the largest α-SMA levels and associated force generation. Validation was performed by comparisons to traction force microscopy studies, which showed very good agreement. Interestingly, only in the highest activation state was strain rate sensitivity observed, which was captured successfully in the simulations. These unique findings demonstrated that only VICs with high levels of αSMA expression exhibited significant viscoelastic effects. Implications of this study include greater insight into the functional role of α-SMA and F-actin in VIC stress fiber function, and the potential for strain rate-dependent effects in pathological states where high levels of α-SMA occur, which appear to be unique to the valvular cellular in vivo microenvironment.
A Single-Degree-of-Freedom Self-Regulated Gravity Balancer for Adjustable Payload1
Authors: Chu Yu-Lin , Kuo Chin-Hsing
Published: December 2016

This paper presents a single-degree-of-freedom (single-DoF) gravity balancer that can deal with variable payload without requesting manual or other auxiliary adjustment. The proposed design is an integration of two mechanism modules, i.e., a standard spring-based statically balanced mechanism and a spring adjusting mechanism. A tensile spring is attached to the statically balanced mechanism for balancing the payload, and its installation points are controlled by two cables, which are driven by the spring adjusting mechanism. When different payloads are applied, the spring adjusting mechanism will act to regulate the spring installation points to suitable places such that the overall potential energy of the mechanism and the (variable) payload remains constant within the workspace of the balancer. This therefore suggests the main novelty of the proposed design where the balancer mechanism can automatically sense and respond the change of the payload without manual adjustment to the balancing mechanism. A prototype is built up and successfully tested for the proposed concept.
Results of Air Barbotage Experiments Simulating Two-Phase Flow in a CANDU End Shield During In-Vessel Retention
Authors: Spencer Justin H.
Published: December 2016

This paper presents the results of experimental investigations into two-phase mass transport in a coarse packed bed representing the Canada Deuterium Uranium (CANDU) end shield. This work contributes to understanding of phenomena impacting in-vessel retention (IVR) during postulated severe accidents in CANDU reactors. The air barbotage technique was used to represent boiling at the calandria tubesheet surface facing the inner cavity of the end shield. Qualitative observations of the near-wall two-phase region were made during air injection. In addition, flow visualization was carried out through the addition of dye to the water. Air flow rate, shielding ball diameter, and cavity dimensions were varied within relevant ranges; and the impact of these parameters on the near-wall region was identified. A brief review of the relevant knowledge base is presented, allowing demonstration of the applicability of the test parameters. The observed phenomena are compared to published results involving similar geometries with capillary porous media.
Novel Fault-Tolerance Indices for Redundantly Actuated Parallel Robots
Authors: Isaksson Mats , Marlow Kristan , Maciejewski Anthony , Eriksson Anders
Published: December 2016

Robots designed for space applications, deep sea applications, handling of hazardous material and surgery should ideally be able to handle as many potential faults as possible. This paper provides novel indices for fault tolerance analysis of redundantly actuated parallel robots. Such robots have the potential for higher accuracy, improved stiffness, and higher acceleration compared to similar-sized serial robots. The faults considered are free-swinging joint failures (FSJFs), defined as a software or hardware fault, preventing the administration of actuator torque on a joint. However, for a large range of robots, the proposed indices are applicable also to faults corresponding to the disappearance of a kinematic chain, for example, a breakage. Most existing fault tolerance indices provide a ratio between a robot's performance after the fault and the performance before the fault. In contrast, the indices proposed in this paper provide absolute measures of a robot's performance under the worst-case faults. The proposed indices are based on two recently introduced metrics for motion/force transmission analysis of parallel robots. Their main advantage is their applicability to parallel robots with arbitrary degrees-of–freedom (DOF), along with their intuitive geometric interpretation. The feasibility of the proposed indices is demonstrated through application on a redundantly actuated planar parallel mechanism.
Biofilm mitigation by drug (gentamicin)-loaded liposomes promoted by pulsed ultrasound
Authors: Ma Dong , Wu Junru
Published: December 2016

The gentamicin-loaded nano-sized liposomes are shown to penetrate into alginate-based Ralstonia insidiosa bacterial biofilms by acoustic streaming generated by moderate pulsed ultrasound (frequency = 2.25 MHz, 10% duty cycle and spatially and temporally averaged intensity, ISATA ≈ 4.4 W/cm2). The liposomes are then burst by the scanned relatively high intensity ultrasound (frequency = 1.1 MHz, 10% duty cycle, the spatially and temporally averaged intensity ISATA ≈ 90 W/cm2) in situ, and the gentamicin solution is released from the liposomes resulting in 72% of Ralstonia insidiosa killing.
Underwater sound localization of pure tones in the median plane by harbor seals (Phoca vitulina)
Authors: Byl Jenny Ann , Miersch Lars , Wieskotten Sven , Dehnhardt Guido
Published: December 2016

In an underwater environment the physical characteristics of sound propagation differ considerably from those in air. For this reason, sound localization underwater is associated with difficulties, especially in the median plane. It was the approach of the present study to investigate whether harbor seals (Phoca vitulina) are able to determine the direction of a tonal signal form above or below in the underwater environment. Minimum audible angles (MAAs) or the angular range in which the animals could localize a pure tone stimulus in the vertical plane were obtained for frequencies from 0.35 up to 16 kHz. Testing was conducted with four male harbor seals in a semi-circle area of 6 m in diameter in about 2.5 m depth, by using a two alternative forced choice method. The results show that harbor seals are able to localize a pure tone in the median plane under water with a high performance for low frequency stimuli between 350 Hz and 2 kHz with MAAs ranging from below 2.5° up to about 25°. For higher frequencies the animals show strong individual differences.
Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes
Authors: Balzarotti Francisco , Eilers Yvan , Gwosch Klaus C. , Gynnå Arvid H. , Westphal Volker , Stefani Fernando D. , Elf Johan , Hell Stefan W.
Published: December 2016

Superresolution imaging in sharper focus

An optical microscope cannot distinguish objects separated by less than half the wavelength of light. Superresolution techniques have broken this “diffraction limit” and provided exciting new insights into cell biology. Still, such techniques hit a limit at a resolution of about 10 nm. Balzarotti
et al.
describe another way of localizing single molecules called MINFLUX (see the Perspective by Xiao and Ha). As in photoactivated localization microscopy and stochastic optical reconstruction microscopy, fluorophores are stochastically switched on and off, but the emitter is located using an excitation beam that is doughnut-shaped, as in stimulated emission depletion. Finding the point where emission is minimal reduces the number of photons needed to localize an emitter. MINFLUX attained ∼1-nanometer precision, and, in single-particle tracking, achieved a 100-fold enhancement in temporal resolution.

Science
, this issue p.
606
; see also p.
582
Strong coupling of a single electron in silicon to a microwave photon
Authors: Mi X. , Cady J. V. , Zajac D. M. , Deelman P. W. , Petta J. R.
Published: December 2016

Inducing strong coupling

Quantum dots, or artificial atoms, are being pursued as prospective building blocks for quantum information processing architectures. Communication with other, distant quantum dots requires strong coupling between photons and the electronic states of the dots. Mi
et al.
used double quantum dots defined in silicon and embedded in a superconducting cavity to achieve such coupling. This demonstration in an industry-relevant material bodes well for the large-scale development of semiconductor-based quantum processors.

Science
, this issue p.
156
Increased Costs Associated with Bloodstream Infections Caused by Multidrug-Resistant Gram-Negative Bacteria Are Due Primarily to Patients with Hospital-Acquired Infections
Authors: Thaden Joshua T. , Li Yanhong , Ruffin Felicia , Maskarinec Stacey A. , Hill-Rorie Jonathan M. , Wanda Lisa C. , Reed Shelby D. , Fowler Vance G.
Published: December 2016

The clinical and economic impacts of bloodstream infections (BSI) due to multidrug-resistant (MDR) Gram-negative bacteria are incompletely understood. From 2009 to 2015, all adult inpatients with Gram-negative BSI at our institution were prospectively enrolled. MDR status was defined as resistance to ≥3 antibiotic classes. Clinical outcomes and inpatient costs associated with the MDR phenotype were identified. Among 891 unique patients with Gram-negative BSI, 292 (33%) were infected with MDR bacteria. In an adjusted analysis, only history of Gram-negative infection was associated with MDR BSI versus non-MDR BSI (odds ratio, 1.60; 95% confidence interval [CI], 1.19 to 2.16;
P
= 0.002). Patients with MDR BSI had increased BSI recurrence (1.7% [5/292] versus 0.2% [1/599];
P
= 0.02) and longer hospital stay (median, 10.0 versus 8.0 days;
P
= 0.0005). Unadjusted rates of in-hospital mortality did not significantly differ between MDR (26.4% [77/292]) and non-MDR (21.7% [130/599]) groups (
P
= 0.12). Unadjusted mean costs were 1.62 times higher in MDR than in non-MDR BSI ($59,266 versus $36,452;
P
= 0.003). This finding persisted after adjustment for patient factors and appropriate empirical antibiotic therapy (means ratio, 1.18; 95% CI, 1.03 to 1.36;
P
= 0.01). Adjusted analysis of patient subpopulations revealed that the increased cost of MDR BSI occurred primarily among patients with hospital-acquired infections (MDR means ratio, 1.41; 95% CI, 1.10 to 1.82;
P
= 0.008). MDR Gram-negative BSI are associated with recurrent BSI, longer hospital stays, and increased mean inpatient costs. MDR BSI in patients with hospital-acquired infections primarily account for the increased cost.
Simvastatin Attenuates Endothelial Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas Cardiomyopathy
Authors: González-Herrera Fabiola , Cramer Allysson , Pimentel Pollyana , Castillo Christian , Liempi Ana , Kemmerling Ulrike , Machado Fabiana S. , Maya Juan D.
Published: December 2016

Current treatments for chronic Chagas cardiomyopathy, a disease with high mortality rates and caused by the protozoan
Trypanosoma cruzi
, are unsatisfactory. Myocardial inflammation, including endothelial activation, is responsible for the structural and functional damage seen in the chronic phase. The clinical efficacy of benznidazole could be improved by decreasing chronic inflammation. Statins, which have anti-inflammatory properties, may improve the action of benznidazole. Here, the action of simvastatin in a murine model of chronic Chagas cardiomyopathy and the link with the production of the proresolving eicosanoid 15-epi-lipoxin A4, produced by 5-lipoxygenase, are evaluated. Simvastatin decreased the expression of the adhesion molecules E-selectin, intracellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1) in
T. cruzi
-infected mice. However, when this drug was administered to 5-lipoxygenase-deficient mice, the anti-inflammatory effect was not observed unless exogenous 15-epi-lipoxin A4 was administered. Thus, in chronic Chagas disease, 5-epi-lipoxin A4 induced by simvastatin treatment could improve the pathophysiological condition of patients by increasing the trypanocidal action of benznidazole.
Establishing Genotypic Cutoff Values To Measure Antimicrobial Resistance in Salmonella
Authors: Tyson Gregory H. , Zhao Shaohua , Li Cong , Ayers Sherry , Sabo Jonathan L. , Lam Claudia , Miller Ron A. , McDermott Patrick F.
Published: December 2016

Whole-genome sequencing (WGS) has transformed our understanding of antimicrobial resistance, helping us to better identify and track the genetic mechanisms underlying phenotypic resistance. Previous studies have demonstrated high correlations between phenotypic resistance and the presence of known resistance determinants. However, there has never been a large-scale assessment of how well resistance genotypes correspond to specific MICs. We performed antimicrobial susceptibility testing and WGS of 1,738 nontyphoidal
Salmonella
strains to correlate over 20,000 MICs with resistance determinants. Using these data, we established what we term genotypic cutoff values (GCVs) for 13 antimicrobials against
Salmonella
. For the drugs we tested, we define a GCV as the highest MIC of isolates in a population devoid of known acquired resistance mechanisms. This definition of GCV is distinct from epidemiological cutoff values (ECVs or ECOFFs), which currently differentiate wild-type from non-wild-type strains based on MIC distributions alone without regard to genetic information. Due to the large number of isolates involved, we observed distinct MIC distributions for isolates with different resistance gene alleles, including for ciprofloxacin and tetracycline, suggesting the potential to predict MICs based on WGS data alone.
Obatoclax Inhibits Alphavirus Membrane Fusion by Neutralizing the Acidic Environment of Endocytic Compartments
Authors: Varghese Finny S. , Rausalu Kai , Hakanen Marika , Saul Sirle , Kümmerer Beate M. , Susi Petri , Merits Andres , Ahola Tero
Published: December 2016

As new pathogenic viruses continue to emerge, it is paramount to have intervention strategies that target a common denominator in these pathogens. The fusion of viral and cellular membranes during viral entry is one such process that is used by many pathogenic viruses, including chikungunya virus, West Nile virus, and influenza virus. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins, was previously determined to have activity against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses, like chikungunya virus (50% effective concentration [EC
50
] = 0.03 μM) and Semliki Forest virus (SFV; EC
50
= 0.11 μM). Obatoclax inhibited viral entry processes in an SFV temperature-sensitive mutant entry assay. A neutral red retention assay revealed that obatoclax induces the rapid neutralization of the acidic environment of endolysosomal vesicles and thereby most likely inhibits viral fusion. Characterization of escape mutants revealed that the L369I mutation in the SFV E1 fusion protein was sufficient to confer partial resistance against obatoclax. Other inhibitors that target the Bcl-2 family of antiapoptotic proteins inhibited neither viral entry nor endolysosomal acidification, suggesting that the antiviral mechanism of obatoclax does not depend on its anticancer targets. Obatoclax inhibited the growth of flaviviruses, like Zika virus, West Nile virus, and yellow fever virus, which require low pH for fusion, but not that of pH-independent picornaviruses, like coxsackievirus A9, echovirus 6, and echovirus 7. In conclusion, obatoclax is a novel inhibitor of endosomal acidification that prevents viral fusion and that could be pursued as a potential broad-spectrum antiviral candidate.
Alternative Protein Sources in the Diet Modulate Microbiota and Functionality in the Distal Intestine of Atlantic Salmon (Salmo salar)
Authors: Gajardo Karina , Jaramillo-Torres Alexander , Kortner Trond M. , Merrifield Daniel L. , Tinsley John , Bakke Anne Marie , Krogdahl Åshild
Published: December 2016

The present study aimed to investigate whether alternative dietary protein sources modulate the microbial communities in the distal intestine (DI) of Atlantic salmon, and whether alterations in microbiota profiles are reflected in modifications in host intestinal function and health status. A 48-day feeding trial was conducted, in which groups of fish received one of five diets: a reference diet in which fishmeal (diet FM) was the only protein source and four experimental diets with commercially relevant compositions containing alternative ingredients as partial replacements of fishmeal, i.e., poultry meal (diet PM), a mix of soybean meal and wheat gluten (diet SBMWG), a mix of soy protein concentrate and poultry meal (diet SPCPM), and guar meal and wheat gluten (diet GMWG). Samples were taken of DI digesta and mucosa for microbial profiling using high-throughput sequencing and from DI whole tissue for immunohistochemistry and expression profiling of marker genes for gut health. Regardless of diet, there were significant differences between the microbial populations in the digesta and the mucosa in the salmon DI. Microbial richness was higher in the digesta than the mucosa. The digesta-associated bacterial communities were more affected by the diet than the mucosa-associated microbiota. Interestingly, both legume-based diets (SBMWG and GMWG) presented high relative abundance of lactic acid bacteria in addition to alteration in the expression of a salmon gene related to cell proliferation (
pcna
). It was, however, not possible to ascertain the cause-effect relationship between changes in bacterial communities and the host's intestinal responses to the diets.

IMPORTANCE
The intestine of cultivated Atlantic salmon shows symptoms of compromised function, which are most likely caused by imbalances related to the use of new feed ingredients. Intestinal microbiota profiling may become in the future a valuable endpoint measurement in order to assess fish intestinal health status and effects of diet. The present study aimed to gain information about whether alternative dietary protein sources modulate the microbial communities in the Atlantic salmon intestine and whether alterations in microbiota profiles are reflected in alterations in host intestinal function and health status. We demonstrate here that there are substantial differences between the intestinal digesta and mucosa in the presence and abundance of bacteria. The digesta-associated microbiota showed clear dependence on the diet composition, whereas mucosa-associated microbiota appeared to be less affected by diet composition. Most important, the study identified bacterial groups associated with diet-induced gut dysfunction that may be utilized as microbial markers of gut health status in fish.
Effects of Actinomycete Secondary Metabolites on Sediment Microbial Communities
Authors: Patin Nastassia V. , Schorn Michelle , Aguinaldo Kristen , Lincecum Tommie , Moore Bradley S. , Jensen Paul R.
Published: December 2016

Marine sediments harbor complex microbial communities that remain poorly studied relative to other biomes such as seawater. Moreover, bacteria in these communities produce antibiotics and other bioactive secondary metabolites, yet little is known about how these compounds affect microbial community structure. In this study, we used next-generation amplicon sequencing to assess native microbial community composition in shallow tropical marine sediments. The results revealed complex communities comprised of largely uncultured taxa, with considerable spatial heterogeneity and known antibiotic producers comprising only a small fraction of the total diversity. Organic extracts from cultured strains of the sediment-dwelling actinomycete genus
Salinispora
were then used in mesocosm studies to address how secondary metabolites shape sediment community composition. We identified predatory bacteria and other taxa that were consistently reduced in the extract-treated mesocosms, suggesting that they may be the targets of allelopathic interactions. We tested related taxa for extract sensitivity and found general agreement with the culture-independent results. Conversely, several taxa were enriched in the extract-treated mesocosms, suggesting that some bacteria benefited from the interactions. The results provide evidence that bacterial secondary metabolites can have complex and significant effects on sediment microbial communities.

IMPORTANCE
Ocean sediments represent one of Earth's largest and most poorly studied biomes. These habitats are characterized by complex microbial communities where competition for space and nutrients can be intense. This study addressed the hypothesis that secondary metabolites produced by the sediment-inhabiting actinomycete
Salinispora arenicola
affect community composition and thus mediate interactions among competing microbes. Next-generation amplicon sequencing of mesocosm experiments revealed complex communities that shifted following exposure to
S. arenicola
extracts. The results reveal that certain predatory bacteria were consistently less abundant following exposure to extracts, suggesting that microbial metabolites mediate competitive interactions. Other taxa increased in relative abundance, suggesting a benefit from the extracts themselves or the resulting changes in the community. This study takes a first step toward assessing the impacts of bacterial metabolites on sediment microbial communities. The results provide insight into how low-abundance organisms may help structure microbial communities in ocean sediments.
The Sinorhizobium (Ensifer) fredii HH103 Nodulation Outer Protein NopI Is a Determinant for Efficient Nodulation of Soybean and Cowpea Plants
Authors: Jiménez-Guerrero Irene , Pérez-Montaño Francisco , Medina Carlos , Ollero Francisco Javier , López-Baena Francisco Javier
Published: December 2016

The type III secretion system (T3SS) is a specialized secretion apparatus that is commonly used by many plant and animal pathogenic bacteria to deliver proteins, termed effectors, to the interior of the host cells. These effectors suppress host defenses and interfere with signal transduction pathways to promote infection. Some rhizobial strains possess a functional T3SS, which is involved in the suppression of host defense responses, host range determination, and symbiotic efficiency. The analysis of the genome of the broad-host-range rhizobial strain
Sinorhizobium fredii
HH103 identified eight genes that code for putative T3SS effectors. Three of these effectors, NopL, NopP, and NopI, are
Rhizobium
specific. In this work, we demonstrate that NopI, whose amino acid sequence shows a certain similarity with NopP, is secreted through the
S. fredii
HH103 T3SS in response to flavonoids. We also determined that NopL can be considered an effector since it is directly secreted to the interior of the host cell as demonstrated by adenylate cyclase assays. Finally, the symbiotic phenotype of single, double, and triple
nopI
,
nopL
, and
nopP
mutants in soybean and cowpea was assayed, showing that NopI plays an important role in determining the number of nodules formed in both legumes and that the absence of both NopL and NopP is highly detrimental for symbiosis.

IMPORTANCE
The paper is focused on three
Rhizobium
-specific T3SS effectors of
Sinorhizobium fredii
HH103, NopL, NopP, and NopI. We demonstrate that
S. fredii
HH103 is able to secrete through the T3SS in response to flavonoids the nodulation outer protein NopI. Additionally, we determined that NopL can be considered an effector since it is secreted to the interior of the host cell as demonstrated by adenylate cyclase assays. Finally, nodulation assays of soybean and cowpea indicated that NopI is important for the determination of the number of nodules formed and that the absence of both NopL and NopP negatively affected nodulation.
Erg4A and Erg4B Are Required for Conidiation and Azole Resistance via Regulation of Ergosterol Biosynthesis in Aspergillus fumigatus
Authors: Long Nanbiao , Xu Xiaoling , Zeng Qiuqiong , Sang Hong , Lu Ling
Published: December 2016

Ergosterol, a fungus-specific sterol enriched in cell plasma membranes, is an effective antifungal drug target. However, current knowledge of the ergosterol biosynthesis process in the saprophytic human fungal pathogen
Aspergillus fumigatus
remains limited. In this study, we found that two endoplasmic reticulum-localized sterol C-24 reductases encoded by both
erg4A
and
erg4B
homologs are required to catalyze the reaction during the final step of ergosterol biosynthesis. Loss of one homolog of Erg4 induces the overexpression of the other one, accompanied by almost normal ergosterol synthesis and wild-type colony growth. However, double deletions of
erg4A
and
erg4B
completely block the last step of ergosterol synthesis, resulting in the accumulation of ergosta-5,7,22,24(28)-tetraenol, a precursor compound of ergosterol. Further studies indicate that
erg4A
and
erg4B
are required for conidiation but not for hyphal growth. Importantly, the Δ
erg4A
Δ
erg4B
mutant still demonstrates wild-type virulence in a compromised mouse model but displays remarkable increased susceptibility to antifungal azoles. Our data suggest that inhibitors of Erg4A and Erg4B may serve as effective candidates for adjunct antifungal agents with azoles.

IMPORTANCE
Knowledge of the ergosterol biosynthesis pathway in the human opportunistic pathogen
A. fumigatus
is useful for designing and finding new antifungal drugs. In this study, we demonstrated that the endoplasmic reticulum-localized sterol C-24 reductases Erg4A and Erg4B are required for conidiation via regulation of ergosterol biosynthesis. Moreover, inactivation of both Erg4A and Erg4B results in hypersensitivity to the clinical guideline-recommended antifungal drugs itraconazole and voriconazole. Therefore, our finding indicates that inhibition of Erg4A and Erg4B might be an effective approach for alleviating
A. fumigatus
infection.