bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of the Staphylococcus aureus nitric oxide reductase (saNOR) reveals its contribution to modulating intracellular NO levels and cellular respiration
Authors: Lewis A. M. , Matzdorf S. S. , Endres J. L. , Windham I. H. , Bayles K. W. , Rice K. C.
Published: February 2015

Staphylococcus aureus nitrosative stress resistance is due in part to flavohemoprotein (Hmp). Although hmp is present in all sequenced S. aureus genomes, 37% of analyzed strains also contain nor, encoding a predicted quinol‐type nitric oxide (NO) reductase (saNOR). DAF‐FM staining of NO‐challenged wild‐type, nor, hmp and nor hmp mutant biofilms suggested that Hmp may have a greater contribution to intracellular NO detoxification relative to saNOR. However, saNOR still had a significant impact on intracellular NO levels and complemented NO detoxification in a nor hmp mutant. When grown as NO‐challenged static (low‐oxygen) cultures, hmp and nor hmp mutants both experienced a delay in growth initiation, whereas the nor mutant's ability to initiate growth was comparable with the wild‐type strain. However, saNOR contributed to cell respiration in this assay once growth had resumed, as determined by membrane potential and respiratory activity assays. Expression of nor was upregulated during low‐oxygen growth and dependent on SrrAB, a two‐component system that regulates expression of respiration and nitrosative stress resistance genes. High‐level nor promoter activity was also detectable in a cell subpopulation near the biofilm substratum. These results suggest that saNOR contributes to NO‐dependent respiration during nitrosative stress, possibly conferring an advantage to nor+ strains in vivo.
Seed morphology of Rhododendron sichotense (Ericaceae): systematic implications
Authors: Koksheeva Inna , Naryshkina Natalia , Kislov Dmitrii
Published: February 2015

The size of Rhododendron sichotense seeds and exotesta cells from 20 populations were studied using a scanning electron microscope (SEM). The results of a correlation analysis showed that seed size depends on bioclimatic factors. As a species marker, we used the exotesta cell elongation coefficient. This characteristic was unresponsive to environmental variables, demonstrating its taxonomic significance. In the centre of the species range, the samples had an exotesta cell elongation coefficient that was typical for the species, but in samples from the far northern and southern parts of the range, where the distribution of R. sichotense meets that of of R. dauricum L. and R. mucronulatum Turcz., respectively, the value of the exotesta cell elongation coefficient was intermediate between these species. Therefore, the exotesta cell elongation coefficient can be recommended for use in the detection of hybridisation areas.
Diagnosis and treatment of depression and cognitive impairment in late life
Authors: Morimoto Sarah Shizuko , Kanellopoulos Dora , Manning Kevin J. , Alexopoulos George S.
Published: February 2015

Cognitive impairment in late‐life depression is prevalent, disabling, and heterogeneous. Although mild cognitive impairment in depression does not usually progress to dementia, accurate assessment of cognition is vital to prognosis and treatment planning. For example, executive dysfunction often accompanies late‐life depression, influences performance across cognitive domains, and is associated with poor antidepressant treatment outcomes. Here, we review how assessment can capture dysfunction across cognitive domains and discuss cognitive trajectories frequently observed in late‐life depression in the context of the neurobiology of this disorder. We also review the efficacy of a sample of interventions tailored to specific cognitive profiles.
The pupil as an indicator of unconscious memory: Introducing the pupil priming effect
Authors: Gomes Carlos Alexandre , Montaldi Daniela , Mayes Andrew
Published: February 2015

We explored whether object behavioral priming and pupil changes occur in the absence of recognition memory. Experiment 1 found behavioral priming for unrecognized objects (Ms) regardless of whether they had been encoded perceptually or conceptually. Using the same perceptual encoding task, Experiment 2 showed greater pupil dilation for Ms than for correct rejections of unstudied objects (CRs) when reaction times were matched. In Experiment 3, there was relatively less pupil dilation for Ms than for similarly matched CRs when objects had been encoded conceptually. Mean/peak pupil dilation for CRs, but not Ms, increased in Experiment 3, in which novelty expectation was also reduced, and the pupillary time course for both Ms and CRs was distinct in the two experiments. These findings indicate that both behavioral and pupil memory occur for studied, but unrecognized stimuli, and suggest that encoding and novelty expectation modulate pupillary memory responses.
DYNAMICS OF REGIONAL NEW FIRM FORMATION IN TURKEY
Authors: Karahasan Burhan Can
Published: February 2015

New firm formation is an important determinant of regional development. Entrepreneurial decisions on location choice are affected by numerous factors. Given the importance of local regional characteristics, this study focuses on the dynamics behind the regional formation of new firms in Turkey using balanced panel data from 1997 to 2006. An initial set of analyses underline the ongoing persistence of the unequal distribution of new firms. Among various factors, results obtained from different panel models suggest the importance of local demand, provincial business cycles, human capital development, and financial availabilities to explain the regional differences of new firm formation in Turkey. These results, which are robust to the inclusion of spatial links, also confirm that the proposed channels are common for manufacturing, services, and trade‐based production.
Typicality effects in picture‐word interference paradigm: An evaluation of the response exclusion hypothesis
Authors: Fang Yanhong , Zhang Jijia , Yin Guanhai , Hu Senqi , Zhang Entao
Published: February 2015

The response exclusion hypothesis suggests that the polarity of semantic effects in the picture‐word interference paradigm is determined by the response‐relevant criteria. Semantic interference effects would be observed when semantically related distractor words satisfy the response‐relevant criteria; otherwise, semantic facilitation effects should be found. The purpose of this study was to further evaluate the response exclusion hypothesis by exploring the typicality effects in pictures naming. In two experiments, pictures of objects were named either in the context of verb distractor words with different typicality of passive functions or in the context of adjective distractor words with different typicality of characteristics. Facilitation effects were observed in context of typical verbs and adjectives, while interference effects were observed in the context of atypical verbs and adjectives. Given that neither typical nor atypical distractor words satisfy the response‐relevant criteria to produce noun, these findings are problematic for the response exclusion hypothesis. Role of syntagmatic relationships in lexical retrieval was invoked to explain present findings.
Confrontation and Beyond: Examining a Stigmatized Target's Use of a Prejudice Reduction Strategy
Authors: Focella Elizabeth S. , Bean Meghan G. , Stone Jeff
Published: February 2015

What can stigmatized individuals do to reduce stereotyping, prejudice, and discrimination when they interact with a biased individual? This paper reviews the social psychological literature that examines how targets can be active agents of prejudice reduction for themselves and their group. The extant literature indicates that a target's direct confrontation of bias can reduce prejudice and discrimination against the target's group but that this strategy can also backlash in the form of increased prejudice and discrimination against the target. Other research indicates that presenting a common‐identity, self‐enhancing feedback, and a self‐affirmation can reduce bias against the target but that they may not reliably change bias against the target's group. We conclude by discussing the need for research on the processes by which stigmatized targets decide to use a given bias‐reduction strategy and on the processes by which specific strategies are effective, either alone or in combination, when delivered by a stigmatized target.
Ocean current intensification during the Cretaceous oceanic anoxic event 2 – evidence from the northern Tethys
Authors: Wohlwend Stephan , Hart Malcolm , Weissert Helmut
Published: February 2015

Mesozoic Oceanic Anoxic Events (OAEs) are expressions of major physical oceanographic changes at times of perturbation of the global carbon cycle. A northern Tethyan record of OAE2 is preserved in expanded Cenomanian–Turonian pelagic limestone sections (Seewen Formation) in Eastern Switzerland. The new carbonate carbon‐isotope stratigraphy extracted from these limestones demonstrates that the OAE2 is condensed in all the studied successions and only the onset of the δ13C excursion (5.0‰) is present. The condensed interval is characterized by dissolution features, which are filled by a glauconite quartz sandstone. This bed is overlain by a well‐sorted sandstone with intercalated limestone pebbles (Götzis Member), which can be compared with palimpsest sands forming today along current‐swept shelves. The wide distribution of this thin sandstone layer within OAE2 indicates that an intense, erosive, east‐west trending shelf current was active during the highest sea level and most extreme carbon‐cycle perturbation of the OAE2.
Effect of Clathrin Light Chains on the Stiffness of Clathrin Lattices and Membrane Budding
Authors: Dannhauser Philip N. , Platen Mitja , Böning Heike , Ungewickell Huberta , Schaap Iwan A.T. , Ungewickell Ernst J.
Published: February 2015

Clathrin‐dependent transport processes require the polymerization of clathrin triskelia into polygonal scaffolds. Together with adapter proteins, clathrin collects cargo and induces membrane bud formation. It is not known to what extent clathrin light chains affect the structural and functional properties of clathrin lattices and the ability of clathrin to deform membranes. To address these issues, we have developed a novel procedure for analyzing clathrin lattice formation on rigid surfaces. We found that lattices can form on adaptor‐coated convex‐, planar‐ and even shallow concave surfaces, but the rate of formation and resistance to thermal dissociation of the lattice are greatly enhanced on convex surfaces. Atomic force microscopy on planar clathrin lattices demonstrates that the stiffness of the clathrin lattice is strictly dependent on light chains. The reduced stiffness of the lattice also compromised the ability of clathrin to generate coated buds on the surface of rigid liposomal membranes.
A novel approach to increasing inventory with the current panel: increasing donation frequency by asking for a different blood product
Authors: Bagot Kathleen L. , Masser Barbara M. , White Katherine M.
Published: February 2015

BACKGROUND

Ongoing shortages of blood products may be addressed through additional donations. However, donation frequency rates are typically lower than medically possible. This preliminary study aims to determine voluntary nonremunerated whole blood (WB) and plasmapheresis donors' willingness, and subsequent facilitators and barriers, to make additional donations of a different type.

STUDY DESIGN AND METHODS

Forty individual telephone interviews were conducted posing two additional donation pattern scenarios: first, making a single and, second, making multiple plasmapheresis donations between WB donations. Stratified purposive sampling was conducted for four samples varying in donation experience: no‐plasma, new‐to‐both‐WB‐and‐plasma, new‐to‐plasma, and plasma donors. Interviews were analyzed yielding excellent (κ values > 0.81) inter‐rater reliability.

RESULTS

Facilitators were more endorsed than barriers for a single but not multiple plasmapheresis donation. More new‐to‐both donors (n = 5) were willing to make multiple plasma donations between WB donations than others (n = 1 each) and identified fewer barriers (n = 3) than those more experienced in donation (n = 8 no plasma, n = 10 new to both, n = 11 plasma). Donors in the plasma sample were concerned about the subsequent reduced time between plasma donations by adding WB donations (n = 3). The no‐plasma and new‐to‐plasma donors were concerned about the time commitment required (n = 3).

CONCLUSION

Current donors are willing to add different product donations but donation history influences their willingness to change. Early introduction of multiple donation types, variation in inventory levels, and addressing barriers will provide blood collection agencies with a novel and cost‐effective inventory management strategy.
Controversies in the use of hydroxyethyl starch solutions in small animal emergency and critical care
Authors: Adamik Katja N. , Yozova Ivayla D. , Regenscheit Nadine
Published: February 2015

Objectives

To (1) review the development and medical applications of hydroxyethyl starch (HES) solutions with particular emphasis on its physiochemical properties; (2) critically appraise the available evidence in human and veterinary medicine, and (3) evaluate the potential risks and benefits associated with their use in critically ill small animals.

Data Sources

Human and veterinary original research articles, scientific reviews, and textbook sources from 1950 to the present.

Human Data Synthesis

HES solutions have been used extensively in people for over 30 years and ever since its introduction there has been a great deal of debate over its safety and efficacy. Recently, results of seminal trials and meta‐analyses showing increased risks related to kidney dysfunction and mortality in septic and critically ill patients, have led to the restriction of HES use in these patient populations by European regulatory authorities. Although the initial ban on the use of HES in Europe has been eased, proof regarding the benefits and safety profile of HES in trauma and surgical patient populations has been requested by these same European regulatory authorities.

Veterinary Data Synthesis

The veterinary literature is limited mostly to experimental studies and clinical investigations with small populations of patients with short‐term end points and there is insufficient evidence to generate recommendations.

Conclusions

Currently, there are no consensus recommendations regarding the use of HES in veterinary medicine. Veterinarians and institutions affected by the HES restrictions have had to critically reassess the risks and benefits related to HES usage based on the available information and sometimes adapt their procedures and policies based on their reassessment. Meanwhile, large, prospective, randomized veterinary studies evaluating HES use are needed to achieve relevant levels of evidence to enable formulation of specific veterinary guidelines.
How sympathetic are your spinal cord circuits?
Authors: Deuchars Susan A.
Published: February 2015

New findings

What is the topic of this review?

This review focuses on the role of gap junctions and interneurones in sympathetic control at the spinal cord level.

What advances does it highlight?

The review considers the importance of these local spinal circuits in contributing to rhythmic autonomic activity and enabling appropriate responses to homeostatic perturbations.

Sympathetic control of end organs relies on the activity of sympathetic preganglionic neurones (SPNs) within the spinal cord. These SPNs exhibit heterogeneity with respect to function, neurochemistry, location, descending inputs and patterns of activity. Part of this heterogeneity is bestowed by local spinal circuitry. Our understanding of the role of these local circuits, including the significance of connections between the SPNs themselves through specialized gap junctions, is patchy. This report focuses on interneurones and gap junctions within these circuits. Gap junctions play a role in sympathetic control; they are located on SPNs in the intermediolateral cell column. Mefloquine, a chemical that blocks these gap junctions, reduces local rhythmic activity in the spinal cord slice and disrupts autonomic control in the working heart–brainstem preparation. The role that these gap junctions may play in health and disease in adult animals remains to be elucidated fully. Presympathetic interneurones are located in laminae V, VII and X and the intermediolateral cell column; those in lamina X are GABAergic and directly inhibit SPNs. The GABAergic inputs onto SPNs exert their effects through activation of synaptic and extrasynaptic receptors, which stabilize the membrane at negative potentials. The GABAergic interneurones contribute to rhythmic patterns of activity that can be generated in the spinal cord, because bicuculline reduces network oscillatory activity. These studies indicate that local spinal cord circuitry is critical in enabling appropriate levels and patterning of activity in sympathetic outflow. We need to understand how these circuits may be harnessed in the situation of spinal cord injury.
Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate‐intensity cycle exercise
Authors: Benda Nathalie M. M. , Seeger Joost P. H. , van Lier Dirk P. T. , Bellersen Louise , van Dijk Arie P. J. , Hopman Maria T. E. , Thijssen Dick H. J.
Published: February 2015

New Findings

What is the central question of this study?

We explored whether heart failure (HF) patients demonstrate different exercise‐induced brachial artery shear rate patterns compared with control subjects.

What is the main finding and its importance?

Moderate‐intensity cycle exercise in HF patients is associated with an attenuated increase in brachial artery anterograde and mean shear rate and skin temperature. Differences between HF patients and control subjects cannot be explained fully by differences in workload. HF patients demonstrate a less favourable shear rate pattern during cycle exercise compared with control subjects.

Repeated elevations in shear rate (SR) in conduit arteries, which occur during exercise, represent a key stimulus to improve vascular function. We explored whether heart failure (HF) patients demonstrate distinct changes in SR in response to moderate‐intensity cycle exercise compared with healthy control subjects. We examined brachial artery SR during 40 min of cycle exercise at a work rate equivalent to 65% peak oxygen uptake in 14 HF patients (65 ± 7 years old, 13 men and one woman) and 14 control subjects (61 ± 5 years old, 12 men and two women). Brachial artery diameter, SR and oscillatory shear index (OSI) were assessed using ultrasound at baseline and during exercise. The HF patients demonstrated an attenuated increase in mean and anterograde brachial artery SR during exercise compared with control subjects (time × group interaction, P = 0.003 and P < 0.001, respectively). Retrograde SR increased at the onset of exercise and remained increased throughout the exercise period in both groups (time × group interaction, P = 0.11). In control subjects, the immediate increase in OSI during exercise (time, P < 0.001) was normalized after 35 min of cycling. In contrast, the increase in OSI after the onset of exercise did not normalize in HF patients (time × group interaction, P = 0.029). Subgroup analysis of five HF patients and five control subjects with comparable workload (97 ± 13 versus 90 ± 22 W, P = 0.59) confirmed the presence of distinct changes in mean SR during exercise (time × group interaction, P = 0.030). Between‐group differences in anterograde/retrograde SR or OSI did not reach statistical significance (time × group interactions, P > 0.05). In conclusion, HF patients demonstrate a less favourable SR pattern during cycle exercise than control subjects, characterized by an attenuated mean and anterograde SR and by increased OSI.
A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice
Authors: Arsenault Dany , Drouin‐Ouellet Janelle , Saint‐Pierre Martine , Petrou Petros , Dubois Marilyn , Kriz Jasna , Barker Roger A. , Cicchetti Antonio , Cicchetti Francesca
Published: February 2015

Key points

We have developed a unique prototype to perform brain stimulation in mice.

This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits).

This new micro‐stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue.

The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation.

Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre‐clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll‐like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2‐fluc‐GFP transgenic mice, which we further corroborated with post‐mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease.
Mechanisms and dynamics of AKAP79/150‐orchestrated multi‐protein signalling complexes in brain and peripheral nerve
Authors: Zhang Jie , Shapiro Mark S.
Published: February 2015

A‐kinase anchoring proteins (AKAPs) have emerged as a converging point of diverse signals to achieve spatiotemporal resolution of directed cellular regulation. With the extensive studies of AKAP79/150 in regulation of ion channel activity, the major questions to be posed centre on the mechanism and functional role of synergistic regulation of ion channels by such signalling proteins. In this review, we summarize recent discoveries of AKAP79/150‐mediated modulation of voltage‐gated neuronal M‐type (KCNQ, Kv7) K+ channels and L‐type CaV1 Ca2+ channels, on both short‐ and longer‐term time scales, highlighting the dynamics of the macromolecular signalling complexes in brain and peripheral nerve We also discuss several models for the possible mechanisms of these multi‐protein assemblies and how they serve the agenda of the neurons in which they occur.
Dynamic synchronization of ongoing neuronal activity across spinal segments regulates sensory information flow
Authors: Contreras‐Hernández E. , Chávez D. , Rudomin P.
Published: February 2015

Key points

We have examined, in the spinal cord of the anaesthetized cat, the relationship between ongoing correlated fluctuations of dorsal horn neuronal activity and state‐dependent activation of inhibitory reflex pathways.

We found that high levels of synchronization between the spontaneous activity of dorsal horn neurones occur in association with the preferential activation of spinal pathways leading to primary afferent depolarization and presynaptic inhibition relative to activation of pathways mediating Ib postsynaptic inhibition.

It is suggested that changes in synchronization of ongoing activity within a distributed network of dorsal horn neurones play a relevant role in the configuration of structured (non‐random) patterns of functional connectivity that shape the interaction of sensory inputs with spinal reflex pathways subserving different functional tasks.

Previous studies on the correlation between spontaneous cord dorsum potentials recorded in the lumbar spinal segments of anaesthetized cats suggested the operation of a population of dorsal horn neurones that modulates, in a differential manner, transmission along pathways mediating Ib non‐reciprocal postsynaptic inhibition and pathways mediating primary afferent depolarization and presynaptic inhibition. In order to gain further insight into the possible neuronal mechanisms that underlie this process, we have measured changes in the correlation between the spontaneous activity of individual dorsal horn neurones and the cord dorsum potentials associated with intermittent activation of these inhibitory pathways. We found that high levels of neuronal synchronization within the dorsal horn are associated with states of incremented activity along the pathways mediating presynaptic inhibition relative to pathways mediating Ib postsynaptic inhibition. It is suggested that ongoing changes in the patterns of functional connectivity within a distributed ensemble of dorsal horn neurones play a relevant role in the state‐dependent modulation of impulse transmission along inhibitory pathways, among them those involved in the central control of sensory information. This feature would allow the same neuronal network to be involved in different functional tasks.
Energy Optimal Control Design for Steer-by-Wire Systems and Hardware-in-the-Loop Simulation Evaluation
Authors: Selçuk Arslan M. , Fukushima Naoto
Published: February 2015

A Steer-By-Wire (SBW) control scheme is proposed for enhancing the lateral stability and handling capability of a super lightweight vehicle by using the energy optimal control method. Tire dissipation power and virtual power, which is the product of yaw moment and the deviation of actual yaw rate from the target yaw rate, were selected as performance measures to be minimized. The SBW control scheme was tested using Hardware-In-the-Loop (HIL) simulation on an SBW test rig. The case studies performed were high-speed rapid lane change, crosswind, and braking-in-a-turn. HIL simulation results showed that the SBW control scheme was able to maintain vehicle stability. The proposed SBW control design taking advantage of the full range steering of front wheel, significantly improves the vehicle handling capability. The results also demonstrate the importance of SBW control for super lightweight vehicles.
Measurements of Loading and Tip Vortex Due to High-Reynolds Number Flow Over a Rigid Lifting Surface
Authors: Krane Michael H. , Meyer Richard S. , Weldon Matthew J. , Elbing Brian , DeVilbiss David W.
Published: February 2015

An experimental study of high-Reynolds number flow over a rigid hydrofoil (David Taylor model basin (DTMB) modified NACA66-009, rectangular planform, aspect ratio (AR = 4, square tip) is presented. The measurements were performed in the Garfield Thomas Water Tunnel at Applied Research Laboratory (ARL) Penn State. Load measurements were performed at ReC = 1.5 × 106 and 2.4 × 106, for angles of attack between −8 deg and +8 deg. Measurements of three components of velocity were performed using stereo particle image velocimetry (SPIV) on a cross-flow plane to resolve the tip vortex flow 0.42 chord lengths downstream of the trailing edge, for four angles of attack ranging from 0.5 deg to 3.5 deg. Nondimensional tip vortex circulation varied weakly with angle of attack. Vortex location in the plane of measurement, relative to the trailing edge, was unchanged for the ranges studied, though the vortex core grew in size with angle of attack. These results are consistent with the finding that the net lift force acts between 45% and 46% span, measured from the root, in that any angle of attack variations in tip vortex strength or radius result in minimal changes in spanwise loading distribution.
Comparison of Experimental and RANS-Based Numerical Studies of the Decay of Grid-Generated Turbulence
Authors: Torrano Ivan , Tutar Mustafa , Martinez-Agirre Manex , Rouquier Anthony , Mordant Nicolas , Bourgoin Mickael
Published: February 2015

This paper presents both experimental and numerical studies of the statistical properties of turbulent flows at moderate Reynolds number (Reλ = 100) in the context of grid-generated turbulence. In spite of the popularity of passive grids as turbulence generators, their design relies essentially on empirical laws. Here, we propose to test the ability of simple numerical simulations to capture the large scale properties (root-mean-square (rms) velocity, turbulence decay, pressure drop, etc.) of the turbulence downstream a passive grid. With this purpose, experimental measurements are compared with the three-dimensional (3D) Reynolds-Averaged Navier–Stokes (RANS) equations based turbulence model simulations. To better modeling of energy cascade of turbulence, different turbulence models, mesh resolutions, and turbulence model constants, which are determined in accordance with the experimentally measured corresponding values, are used. Both qualitative and quantitative comparisons are made with the experimental data to further assess the accuracy and capability of present numerical techniques for their use in different aerodynamic applications at moderate Re number.
Comment on “A promiscuous intermediate underlies the evolution of LEAFY DNA binding specificity”
Authors: Brunkard Jacob O. , Runkel Anne M. , Zambryski Patricia C.
Published: February 2015

Sayou
et al
. (Reports, 7 February 2014, p. 645) proposed a new model for evolution of transcription factors without gene duplication, using LEAFY as an archetype. Their proposal contradicts the evolutionary history of plants and ignores evidence that LEAFY evolves through gene duplications. Within their data set, we identified a moss with multiple LEAFY orthologs, which contests their model and supports that LEAFY evolves through duplications.
Response to Comment on “A promiscuous intermediate underlies the evolution of LEAFY DNA binding specificity”
Authors: Brockington Samuel F. , Moyroud Edwige , Sayou Camille , Monniaux Marie , Nanao Max H. , Thévenon Emmanuel , Chahtane Hicham , Warthmann Norman , Melkonian Michael , Zhang Yong , Wong Gane Ka-Shu , Weigel Detlef , Dumas Renaud , Parcy François
Published: February 2015

Brunkard
et al
. propose that the identification of novel
LEAFY
sequences contradicts our model of evolution through promiscuous intermediates. Based on the debate surrounding land plant phylogeny and on our analysis of these interesting novel sequences, we explain why there is no solid evidence to disprove our model.
Origin of dramatic oxygen solute strengthening effect in titanium
Authors: Yu Qian , Qi Liang , Tsuru Tomohito , Traylor Rachel , Rugg David , Morris J. W. , Asta Mark , Chrzan D. C. , Minor Andrew M.
Published: February 2015

Screw dislocations: A hard case to crack

The motion of dislocations or defects in a metal influences its strength and toughness. If these defects can be “pinned” by adding alloying elements, it should be possible to create a stronger alloy. It was thought that there shouldn't be much of an interaction between screw dislocations and any alloying elements. However, Yu
et al.
show that for α-Ti, the profound hardening effect of oxygen is due to the strong interactions with the core of the dislocations. First-principles calculations reveal that distortion of the interstitial sites at the dislocation core creates a very strong but short-range repulsion for oxygen atoms.

Science
, this issue p.
635
Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology
Authors: Creed Meaghan , Pascoli Vincent Jean , Lüscher Christian
Published: February 2015

Reversing cocaine-evoked behavior in mice

Therapeutic optogenetic protocols are highly effective at reversing symptoms in animal models of neuropsychiatric disease. However, translating these protocols into the clinic is challenging because we have not yet made the technical leap required to perform effective optogenetic stimulation in primates. Creed
et al.
tested whether it would be possible to circumvent these challenges by avoiding the problem altogether. They adjusted an existing therapeutic approach—deep brain stimulation—to mimic an effective optogenetic stimulation protocol to treat a mouse model of cocaine addiction.

Science
, this issue p.
659
Termite mounds can increase the robustness of dryland ecosystems to climatic change
Authors: Bonachela Juan A. , Pringle Robert M. , Sheffer Efrat , Coverdale Tyler C. , Guyton Jennifer A. , Caylor Kelly K. , Levin Simon A. , Tarnita Corina E.
Published: February 2015

Termites can stabilize tropical grasslands

Spotty vegetation patterns in tropical savannas and grasslands can be a warning sign of imminent desertification. However, Bonachela
et al.
find that termites can also produce spotty patterns. Their theoretical study, confirmed by field data from Kenya, shows that patterns produced by termite mounds are not harbingers of desertification. Indeed, the presence of termites buffers these ecosystems against climate change.

Science
, this issue p.
651
Undergraduate research experiences: Impacts and opportunities
Authors: Linn Marcia C. , Palmer Erin , Baranger Anne , Gerard Elizabeth , Stone Elisa
Published: February 2015

Assessing the value of undergraduate research

Undergraduate research experiences often engender enthusiasm in the students involved, but how useful are they in terms of enhancing student learning? Linn
et al.
review studies that focus on the effectiveness of undergraduate research programs. Undergraduate research experiences in a class were distinguished from those involving individualized participation in a research program. Mentoring emerges as both an important component of a successful experience and a target for improvement.

Science
, this issue
10.1126/science.1261757
Seafloor grooves record the beat of the ice ages
Authors: Hand Eric
Published: February 2015

Sea level changes influence the underwater eruptions that build abyssal hills.
U.S. House reveals ambitious biomedical innovation plan
Authors: Servick Kelly
Published: February 2015

Lawmakers seek feedback on long-awaited “21st Century Cures” proposal.
Part 2: Targeting Cancer Pathways: The Tumor Microenvironment
Authors: Jain Rakesh K. , Sharma Padmanee
Published: February 2015

This webinar is the second in a series focusing on the cancer pathways that support tumor development, the emerging research in identifying and targeting these pathways, and innovations in the development of increasingly effective cancer therapy options. Recent advances in our understanding of cancer have revealed that the disease cannot be understood through simple analysis of genetic mutations within cancerous cells. Instead, tumors should be considered complex tissues in which the cancer cells communicate with the surrounding cellular microenvironment and evolve traits that promote their own survival. Here, we will explore how the tumor microenvironment promotes oncogenic progression, while protecting the tumor from therapeutic intervention. By better understanding the tumor microenvironment we can develop strategies and treatment options to neutralize its oncogenic influence and more effectively attack the tumor itself.

View the Webinar
Surrounded by science
Life on Display Revolutionizing U.S. Museums of Science and Natural History in the Twentieth Century
Karen A. Rader and Victoria E. M. Cain
University of Chicago Press, 2014. 481 pp.
Authors: Johnson Kirk R.
Published: February 2015

Tracing the evolution of modern museums of science and natural history
Inflammation-induced disruption of SCS macrophages impairs B cell responses to secondary infection
Authors: Gaya Mauro , Castello Angelo , Montaner Beatriz , Rogers Neil , Reis e Sousa Caetano , Bruckbauer Andreas , Batista Facundo D.
Published: February 2015

Bacterial infection breaks the lymph node barrier

During infections, lymph nodes are command central. Fragments from invading pathogens enter lymph nodes through the lymph. There, specialized cells called subcapsular sinus (SCS) macrophages capture these antigens and use them to initiate humoral immunity. Despite being such important players, Gaya
et al.
report that in mice, infection throws these organized sentinels into disarray (see the Perspective by Buzsaki). Disrupting SCS macrophages had important consequences: Bacterially infected mice could not respond as efficiently to a subsequent viral infection.

Science
, this issue p.
667
; see also p.
612
Direct observation and kinetics of a hydroperoxyalkyl radical (QOOH)
Authors: Savee John D. , Papajak Ewa , Rotavera Brandon , Huang Haifeng , Eskola Arkke J. , Welz Oliver , Sheps Leonid , Taatjes Craig A. , Zádor Judit , Osborn David L.
Published: February 2015

Catching a glimpse of the elusive QOOH

It's straightforward to write down the net combustion reaction: Oxygen reacts with hydrocarbons to form water and carbon dioxide. The details of how all the bonds break and form in succession are a great deal more complicated. Savee
et al.
now report direct detection of a long-postulated piece of the puzzle, a so-called QOOH intermediate. This structure results from bound oxygen stripping a hydrogen atom from carbon, leaving a carbon-centered radical behind. The study explores the influence of the hydrocarbon's unsaturation on the stability of QOOH, which has implications for both combustion and tropospheric oxidation chemistry.

Science
, this issue p.
643
Breaking bad science
I Think You'll Find It's a Bit More Complicated Than That
Ben Goldacre
Fourth Estate, 2014. 496 pp.
Authors: Best Joel
Published: February 2015

A physician's quest to expose the many misuses of science in the media
Taking temperature at the nanoscale
Authors: Colliex Christian
Published: February 2015

A local probe technique can determine temperature with nanometer-scale resolution

[Also see Report by

Mecklenburg
et al.

]
There goes the macrophage neighborhood
Authors: Hickman Heather D.
Published: February 2015

Migrating dendritic cells disrupt lymph node macrophages and limit the immune response to secondary infection

[Also see Report by

Gaya
et al.

]
Streptococcus pneumoniae Serotype 1 Burden in the African Meningitis Belt: Exploration of Functionality in Specific Antibodies
Authors: Blumental S. , Moïsi J. C. , Roalfe L. , Zancolli M. , Johnson M. , Burbidge P. , Borrow R. , Yaro S. , Mueller J. E. , Gessner B. D. , Goldblatt D.
Published: February 2015

Streptococcus pneumoniaeserotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3S. pneumoniaeserotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ≥ 8) compared to UK subjects (12% versus 2%,P< 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P< 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.
Detection of Pathogen-Specific Antibodies by Loop-Mediated Isothermal Amplification
Authors: Burbulis Ian E. , Yamaguchi Kumiko , Nikolskaia Olga V. , Prigge Sean T. , Magez Stefan , Bisser Sylvie , Reller Megan E. , Grab Dennis J.
Published: February 2015

Loop-mediated isothermal amplification (LAMP) is a method for enzymatically replicating DNA that has great utility for clinical diagnosis at the point of care (POC), given its high sensitivity, specificity, speed, and technical requirements (isothermal conditions). Here, we adapted LAMP for measuring protein analytes by creating a protein-DNA fusion (referred to here as a “LAMPole”) that attaches oligonucleotides (LAMP templates) to IgG antibodies. This fusion consists of a DNA element covalently bonded to an IgG-binding polypeptide (protein L/G domain). In our platform, LAMP is expected to provide the most suitable means for amplifying LAMPoles for clinical diagnosis at the POC, while quantitative PCR is more suitable for laboratory-based quantification of antigen-specific IgG abundance. As proof of concept, we measured serological responses to a protozoan parasite by quantifying changes in solution turbidity in real time. We observed a >6-log fold difference in signal between sera from vaccinated versus control mice and in a clinical patient sample versus a control. We assert that LAMPoles will be useful for increasing the sensitivity of measuring proteins, whether it be in a clinical laboratory or in a field setting, thereby improving acute diagnosis of a variety of infections.
Fusobacterium nucleatum Subspecies Identification by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Nie Shuping , Tian Baoyu , Wang Xiaowei , Pincus David H. , Welker Martin , Gilhuley Kathleen , Lu Xuedong , Han Yiping W. , Tang Yi-Wei
Published: February 2015

We explored the use of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for identification of
Fusobacterium nucleatum
subspecies. MALDI-TOF MS spectra of five
F. nucleatum
subspecies (
animalis
,
fusiforme
,
nucleatum
,
polymorphum
, and
vincentii
) were analyzed and divided into four distinct clusters, including subsp.
animalis
,
nucleatum
,
polymorphum
, and
fusiforme
/
vincentii
. MALDI-TOF MS with the modified SARAMIS database further correctly identified 28 of 34
F. nucleatum
clinical isolates to the subspecies level.
Differential Single Nucleotide Polymorphism-Based Analysis of an Outbreak Caused by Salmonella enterica Serovar Manhattan Reveals Epidemiological Details Missed by Standard Pulsed-Field Gel Electrophoresis
Authors: Scaltriti Erika , Sassera Davide , Comandatore Francesco , Morganti Marina , Mandalari Carmen , Gaiarsa Stefano , Bandi Claudio , Zehender Gianguglielmo , Bolzoni Luca , Casadei Gabriele , Pongolini Stefano
Published: February 2015

We retrospectively analyzed a rare
Salmonella enterica
serovar Manhattan outbreak that occurred in Italy in 2009 to evaluate the potential of new genomic tools based on differential single nucleotide polymorphism (SNP) analysis in comparison with the gold standard genotyping method, pulsed-field gel electrophoresis. A total of 39 isolates were analyzed from patients (
n
= 15) and food, feed, animal, and environmental sources (
n
= 24), resulting in five different pulsed-field gel electrophoresis (PFGE) profiles. Isolates epidemiologically related to the outbreak clustered within the same pulsotype, SXB_BS.0003, without any further differentiation. Thirty-three isolates were considered for genomic analysis based on different sets of SNPs, core, synonymous, nonsynonymous, as well as SNPs in different codon positions, by Bayesian and maximum likelihood algorithms. Trees generated from core and nonsynonymous SNPs, as well as SNPs at the second and first plus second codon positions detailed four distinct groups of isolates within the outbreak pulsotype, discriminating outbreak-related isolates of human and food origins. Conversely, the trees derived from synonymous and third-codon-position SNPs clustered food and human isolates together, indicating that all outbreak-related isolates constituted a single clone, which was in line with the epidemiological evidence. Further experiments are in place to extend this approach within our regional enteropathogen surveillance system.
Diagnostic Accuracy of Presepsin (sCD14-ST) for Prediction of Bacterial Infection in Cerebrospinal Fluid Samples from Children with Suspected Bacterial Meningitis or Ventriculitis
Authors: Stubljar David , Kopitar Andreja Natasa , Groselj-Grenc Mojca , Suhadolc Kristina , Fabjan Teja , Skvarc Miha
Published: February 2015

Children with temporary external ventricular drains (EVD) are prone to nosocomial infections. Diagnosis of bacterial meningitis and ventriculitis in these children is challenging due to frequent blood contamination of cerebrospinal fluid (CSF) and the presence of chemical ventriculitis. The aim of this study was to compare diagnostic accuracy of presepsin (sCD14-ST), a novel biomarker of bacterial infection in CSF, to predict bacterial infection in comparison to the accuracy of established biomarkers like those demonstrated in biochemical analysis of CSF. We conducted a prospective study with 18 children with suspected bacterial meningitis or ventriculitis who had 66 episodes of disease. CSF samples were taken from external ventricular drainage. We measured presepsin in CSF, as well as CSF leukocyte count, glucose, and proteins. CSF was also taken to prove bacterial infection with culture methods or with 16S rRNA gene broad-range PCR (SepsiTest; Molzym, Germany). Infection was clinically confirmed in 57 (86%) episodes of suspected meningitis or ventriculitis. Chemical ventriculitis was diagnosed in 9 (14%) episodes of suspected meningitis or ventriculitis. Diagnostic accuracies presented as area under the curve (AUC) for sCD14-ST, leukocytes, and proteins measured in CSF were 0.877 (95% confidence interval [CI], 0.793 to 0.961), 0.798 (95% CI, 0.677 to 0.920), and 0.857 (95% CI, 0.749 to 0.964), respectively. With CSF culture, we detected bacteria in 17 samples, compared to 37 detected with broad-range PCR. It was found that presepsin was present at a significantly higher level in children with clinically proven ventriculitis than in those without meningitis or ventriculitis. Diagnostic accuracies of presepsin were superior to those of leukocytes or proteins in CSF. Presepsin-guided 16S rRNA gene PCR could be used in everyday clinical practice to improve etiological diagnosis of meningitis and ventriculitis and to prescribe more appropriate antibiotics.
Development of a Peptide Nucleic Acid-Based Multiprobe Real-Time PCR Method Targeting the
hsp65
Gene for Differentiation among Mycobacterium abscessus Strains
Authors: Kim Kijeong , Kim Byoung-Jun , Shim Tae Sun , Hong Seok-Hyun , Kook Yoon-Hoh , Kim Bum-Joon
Published: February 2015

Recently, the need to distinguish between members of the
Mycobacterium abscessus
group has gained increasing attention. Here, we introduced a novel peptide nucleic acid (PNA) real-time PCR method targeting the
hsp65
gene in order to distinguish between four subspecies within the
M. abscessus
group (
M. abscessus
and 3 types of
M. massiliense
).