bluuebunny/crossref_metadata_2025 huggingface dataset:
RNAi‐based functional analysis of yellow‐e in Tribolium castaneum
Authors: Noh Mi Young , Kanost Michael R. , Muthukrishnan Subbaratnam , Beeman Richard W. , Kramer Karl J. , Arakane Yasyuki
Published: November 2011

Pigmentation/melanization is an important physiological event in insect development and is involved in cuticle tanning, wound healing and encapsulation as a defensive response as well as in egg chorion hardening. “Yellow” protein (dopachrome conversion enzyme, DCE) is involved in the melanin biosynthetic pathway and significantly accelerates pigmentation and melanization reactions. Recent studies have suggested that yellow is a rapidly evolving gene family generating functionally diverse paralogs. However, the exact physiological functions of several yellow genes are still not understood. Tribolium castaneum (Tc) is an excellent experimental insect to determine the roles of individual yellow genes because it is possible to carry out RNA interference (RNAi) experiments by injecting gene‐specific double‐stranded RNAs (dsRNAs) into insects at all developmental stages.

Injection of dsRNAs for Tcyellow‐e (TcY‐e) into last instar larvae had no effect on larval‐pupal molting, and the resulting pupae developed normally. The pupal cuticle including the setae, gin traps and urogomphi showed normal tanning. Adult cuticle could also be viewed through the translucent pupal cuticle. Adult cuticle tanning including the head, mandibles and legs was initiated on schedule (pupal day 4‐5), indicating that TcY‐e is not required for pupal or adult cuticle pigmentation in T. castaneum. The subsequent pupal‐adult molt, however, was adversely affected. Although pupal cuticle apolysis and slippage were evident, some of the adults (∼20%) were unable to shed their exuvium and died entrapped in their pupal cuticle. In addition, the resulting adults rapidly became completely desiccated. Failure of the pupal‐adult molt and desiccation‐induced mortality were prevented by maintaining dsRNA TcY‐e‐treated insects at 100% relative humidity (rh). When the humidity‐rescued adults were subsequently moved from 100% rh to 50% rh, they quickly desiccated and died (wild‐type insects thrive throughout development at 50% rh). These results suggest that TcY‐e has a “critical waterproofing” function for cuticle rather than cuticle pigmentation.
“Made in Germany”: The Politics of Teaching German Popular Culture in the Twenty‐First Century
Authors: Kahnke Corinna , Stehle Maria
Published: November 2011

In North American universities, pop culture increasingly appears in the German Studies classroom to “spice up” the curriculum. But what is conveyed and taught and how is it inserted into the curriculum and into the US cultural context? This article explores three examples of popular culture in the German Studies classroom: representations of the Berlin Republic in Good Bye Lenin! and Das Leben der Anderen, Fatih Akin's Gegen die Wand, and songs of the band Rammstein. We argue for an approach that encourages students to explore the politics of national culture in a global context and emphasizes the tensions and contingencies in the materials presented.
Competition, Connection, and Collaboration in Smaller German Programs
Authors: Braunbeck Helga G.
Published: November 2011

The MLA Report on “Foreign Languages and Higher Education: New Structures for a Changed World” has been criticized for focusing its proposals on large German programs. This article attempts to show how some of its recommendations can also be implemented in smaller language programs. These programs exist within a network of relations to other academic programs in their institution with which they both compete and collaborate in order to perform and grow, such as the proliferating International Studies major. Inter‐institutional collaboration can also open up opportunities for richer course offerings than what one small German program could provide. Designing a curriculum that encourages students, especially those from the science and technology disciplines, to double major in German Studies and achieve a high level of proficiency, includes components such as flexible groups of electives, mandatory study abroad or internship abroad, and courses tailored to a student audience interested in science and technology. This includes cultural studies courses that follow a model of interdisciplinarity with the potential for connections with other disciplines. In this article these are explored and illustrated with examples from a course on “Green Germany.” Finally, measures of success are addressed, including ways that even a small German Studies program can establish and maintain its relevance and value in a range of institutional contexts.
Collection of Peripheral Blood CD34+ Progenitor Cells from Healthy Dogs and Dogs Diagnosed with Lymphoproliferative Diseases Using a Baxter‐Fenwal CS‐3000 Plus Blood Cell Separator
Authors: Suter S.E.
Published: November 2011

Background

Canine peripheral blood mononuclear cell (PBMC) apheresis using a Baxter‐Fenwal CS‐3000 Plus automated blood cell separator has not been reported.

Objective

To determine the feasibility and safety of using a CS‐3000 Plus blood cell separator with a small volume separation container holder (SVSCH) and small volume collection chamber (SVCC) to harvest canine PBMCs from dogs weighing <50 kg.

Animals

Eight healthy mongrel dogs and 11 client‐owned dogs in clinical remission for lymphoproliferative diseases (LPD).

Methods

In this prospective study, aphereses were performed using a Baxter‐Fenwal CS‐3000 Plus blood cell separator, with or without recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) treatment.

Results

Aphereses from 6 healthy dogs given rhG‐CSF yielded an average of 1.1 × 107 ± 8.2 × 106 CD34+ cells/kg. Aphereses from LPD dogs given rhG‐CSF yielded an average of 5.4 × 106 ± 3.25 × 106 CD34+ cells/kg (P = .17). Higher hematocrit in both groups of dogs receiving rhG‐CSF correlated with an increased number of CD34+ cells/kg harvested (healthy, P = .04; LPD, P = .05). Apheresis was well tolerated by all dogs.

Conclusions and Clinical Importance

Canine PBMC apheresis using the Baxter‐Fenwal CS‐3000 Plus cell separator with an SVSCH and SVCC is a feasible and safe option for harvesting an adequate number of CD34+ peripheral blood progenitor cells from dogs weighing ≥17 kg for hematopoietic cell transplantation.
Intrinsic morphological diversity of thick‐tufted layer 5 pyramidal neurons ensures robust and invariant properties of in silico synaptic connections
Authors: Ramaswamy Srikanth , Hill Sean L. , King James G. , Schürmann Felix , Wang Yun , Markram Henry
Published: November 2011

Non‐technical summary  Pyramidal neurons are output neurons of the neocortex. The thick‐tufted layer 5 (TTL5) pyramidal neurons are one of the most extensively studied neocortical cell types and are characterized by an exquisite morphological structure. Despite their characteristic morphology, TTL5 neurons in the neocortical microcircuit display an intrinsic diversity that renders each neuron morphologically unique. In order to investigate the functional significance of this intrinsic morphological diversity, we reconstructed networks of TTL5 neurons through a detailed computer model and compared the properties of modelled synaptic connections against experimental data. We found that the average synaptic properties of modelled connections between TTL5 neurons closely matched experimental observations and remained unaltered by changes to several parameters at the local network level. These results show that the intrinsic morphological diversity of TTL5 neurons is a mechanism to ensure that the average synaptic properties are robust to changes at the local network level.
Lobule‐specific membrane excitability of cerebellar Purkinje cells
Authors: Kim Chang‐Hee , Oh Seung‐Ha , Lee Jun Ho , Chang Sun O , Kim Jun , Kim Sang Jeong
Published: November 2011

Non‐technical summary  Cerebellar vermis consists of 10 lobules, and each lobule receives different sensory information. Afferent inputs are integrated in cerebellar Purkinje cells (PCs) which are the sole output of the cerebellar cortex. We show that intrinsic membrane properties are widely different between PCs in the spinocerebellum (lobules III–V) and vestibulocerebellum (lobule X).
Scattering of Solitary Waves and Excitation of Transient Breathers in Granular Media by Light Intruders and No Precompression
Authors: Starosvetsky Yuli , Jayaprakash K. R. , Vakakis Alexander F.
Published: November 2011

We analyze the dynamics of strongly nonlinear granular chains of beads in Hertzian contact with light intruders. We show that the interactions of the light intruders with solitary pulses propagating through the granular medium can be approximately studied by reduced models of the intruders with only their neighboring beads under similar excitation conditions. Studying the reduced models, we identify weakly and strongly nonlinear regimes in the dynamics, depending on the degree of compression between beads and on the occurrence of separation between neighboring beads leading to collisions. We analyze weakly and strongly nonlinear oscillatory regimes of the intruder dynamics by multiple-scale analysis, and by applying special nonsmooth coordinate transformations. When separation between beads occurs, localized transient breathers are excited, corresponding to repeated collisions of an intruder with its neighbors. This leads to high-frequency scattering energy, and to radiation of energy in the granular medium in the form of low-amplitude slowly modulated oscillatory pulses. We find that repeated excitation of localized transient breathers by an array of periodically placed intruders can result in drastic reduction of the amplitude of a solitary wave propagating through the granular medium. This indicates that this type of granular media can be designed as effective shock attenuators.
Development of a Force-Driven Distractor for Distraction Osteogenesis
Authors: Wee Jinyong , Akins Robert E. , Mackenzie William G. , Seliktar Rahamim , Levine David G. , Richardson Dean W. , Dodge George R. , Rahman Tariq
Published: November 2011

Distraction osteogenesis is a routine surgical procedure to lengthen a long bone. A fixed lengthening rate is typically used. We investigate measuring forces continuously and producing a variable distraction rate. A motorized distractor was instrumented with a load cell to measure the forces developed in a limb during distraction osteogenesis. The motor moves 2.6 μm at each step, with a variable frequency depending on the distraction rate. The forces were measured every 15 s and used to change the rate on the autodistractor. The autodistractor, load cell, data logger, controller, and battery pack were all mounted on a monolateral rail fixator, which was tested on a sheep that underwent tibial lengthening. Results show the feasibility of continually recording forces in vivo. The lengthening rate changed automatically, based around a threshold force of 300 N. Findings indicate that force readings are feasible and practical with a simple device. Force determination may provide an additional means to evaluate tissue integrity in real-time and away from the clinic. An automatic variable rate device could improve limb lengthening.
Experimental analysis for process control in hybrid lithography
Authors: Dhima Khalid , Steinberg Christian , Möllenbeck Saskia , Mayer Andre , Wang Si , Sheer Hella-Christin
Published: November 2011

The positive tone resist AZ 1505 is characterized with respect to hybrid lithography that uses thermal nanoimprint lithography to define the nanometric part of a lithography pattern in a first step, followed by optical lithography to define the micron-scaled patterns in the same resist layer in a second step. The parameters investigated are glass temperature and sensitivity (dose curves), both after thermal loading in a typical imprint sequence. The glass transition of the multicomponent resist formulation is derived from stress measurements and the dose curves are evaluated from development rate monitoring via laser interferometry at 532 nm. The results show that both parameters are affected by thermal loading, but adequate choice of the processing parameters makes it possible to compensate for the thermal degradation of the photoresist as long as the imprint temperature chosen does not exceed 130 °C. Based on the characterization results, successful hybrid lithography and lift-off has been demonstrated with AZ 1505.
Improvements to the methods used to measure bubble attenuation using an underwater acoustical resonator
Authors: Czerski Helen , Vagle Svein , Farmer David M. , Hall-Patch Nick
Published: November 2011

Active acoustic techniques are commonly used to measure oceanic bubble size distributions, by inverting the bulk acoustical properties of the water (usually the attenuation) to infer the bubble population. Acoustical resonators have previously been used to determine attenuation over a wide range of frequencies (10–200 kHz) in a single measurement, corresponding to the simultaneous measurement of a wide range of bubble sizes (20–300 μm radii). However, there is now also considerable interest in acquiring measurements of bubbles with radii smaller than 16 μm, since these are thought to be important for ocean optics and as tracers for near-surface flow. To extend the bubble population measurement to smaller radii, it is necessary to extend the attenuation measurements to higher frequencies. Although the principles of resonator operation do not change as the frequency increases, the assumptions previously made during the spectral analysis may no longer be valid. In order to improve the methods used to calculate attenuation from acoustical resonator outputs, a more complete analysis of the resonator operation is presented here than has been published previously. This approach allows for robust attenuation measurements over a much wider frequency range and enables accurate measurements from lower-quality spectral peaks.
Similarities in echolocation strategy and click characteristics between a Pseudorca crassidens and a Tursiops truncatus
Authors: Ibsen Stuart D. , Krause-Nehring Jacqueline , Nachtigall Paul E. , Au Whitlow W. L. , Breese Marlee
Published: November 2011

A previous comparative analysis of normalized click amplitude spectra from a Tursiops truncatus has shown that those frequencies with the lowest click-to-click variability in spectral content were the frequencies the animal paid attention to during target discrimination tasks. In that case, the dolphin only paid attention to the frequency range between 29–42 kHz which had a significantly higher degree of consistency in spectral content than frequencies above 42 kHz. Here it is shown that despite their morphological and behavioral differences, this same pattern of consistency was used by a Pseudorca crassidens performing a similar discrimination task. This comparison between species provides a foundation for using spectral level variability to determine the frequencies most important for echolocation in rare species and non-captive animals. Such results provide key information for successful management.
Model for the dynamics of two interacting axisymmetric spherical bubbles undergoing small shape oscillations
Authors: Kurihara Eru , Hay Todd A. , Ilinskii Yurii A. , Zabolotskaya Evgenia A. , Hamilton Mark F.
Published: November 2011

Interaction between acoustically driven or laser-generated bubbles causes the bubble surfaces to deform. Dynamical equations describing the motion of two translating, nominally spherical bubbles undergoing small shape oscillations in a viscous liquid are derived using Lagrangian mechanics. Deformation of the bubble surfaces is taken into account by including quadrupole and octupole perturbations in the spherical-harmonic expansion of the boundary conditions on the bubbles. Quadratic terms in the quadrupole and octupole amplitudes are retained, and surface tension and shear viscosity are included in a consistent manner. A set of eight coupled second-order ordinary differential equations is obtained. Simulation results, obtained by numerical integration of the model equations, exhibit qualitative agreement with experimental observations by predicting the formation of liquid jets. Simulations also suggest that bubble-bubble interactions act to enhance surface mode instability.
A reduced-order, single-bubble cavitation model with applications to therapeutic ultrasound
Authors: Kreider Wayne , Crum Lawrence A. , Bailey Michael R. , Sapozhnikov Oleg A.
Published: November 2011

Cavitation often occurs in therapeutic applications of medical ultrasound such as shock-wave lithotripsy (SWL) and high-intensity focused ultrasound (HIFU). Because cavitation bubbles can affect an intended treatment, it is important to understand the dynamics of bubbles in this context. The relevant context includes very high acoustic pressures and frequencies as well as elevated temperatures. Relative to much of the prior research on cavitation and bubble dynamics, such conditions are unique. To address the relevant physics, a reduced-order model of a single, spherical bubble is proposed that incorporates phase change at the liquid-gas interface as well as heat and mass transport in both phases. Based on the energy lost during the inertial collapse and rebound of a millimeter-sized bubble, experimental observations were used to tune and test model predictions. In addition, benchmarks from the published literature were used to assess various aspects of model performance. Benchmark comparisons demonstrate that the model captures the basic physics of phase change and diffusive transport, while it is quantitatively sensitive to specific model assumptions and implementation details. Given its performance and numerical stability, the model can be used to explore bubble behaviors across a broad parameter space relevant to therapeutic ultrasound.
Bubble dynamics in a standing sound field: The bubble habitat
Authors: Koch P. , Kurz T. , Parlitz U. , Lauterborn W.
Published: November 2011

Bubble dynamics is investigated numerically with special emphasis on the static pressure and the positional stability of the bubble in a standing sound field. The bubble habitat, made up of not dissolving, positionally and spherically stable bubbles, is calculated in the parameter space of the bubble radius at rest and sound pressure amplitude for different sound field frequencies, static pressures, and gas concentrations of the liquid. The bubble habitat grows with static pressure and shrinks with sound field frequency. The range of diffusionally stable bubble oscillations, found at positive slopes of the habitat-diffusion border, can be increased substantially with static pressure.
Coherence masking protection for mid-frequency formants by adults and children
Authors: Tarr Eric , Nittrouer Susan
Published: November 2011

Coherence masking protection (CMP) refers to the phenomenon in which a target formant is labeled at lower signal-to-noise levels when presented with a stable cosignal consisting of two other formants than when presented alone. This effect has been reported primarily for adults with first-formant (F1) targets and F2/F3 cosignals, but has also been found for children, in fact in greater magnitude. In this experiment, F2 was the target and F1/F3 was the cosignal. Results showed similar effects for each age group as had been found for F1 targets. Implications for auditory prostheses for listeners with hearing loss are discussed.
Wave field synthesis of moving virtual sound sources with complex radiation properties
Authors: Ahrens Jens , Spors Sascha
Published: November 2011

An approach to the synthesis of moving virtual sound sources with complex radiation properties in wave field synthesis is presented. The approach exploits the fact that any stationary sound source of finite spatial extent radiates spherical waves at sufficient distance. The angular dependency of the radiation properties of the source under consideration is reflected by the amplitude and phase distribution on the spherical wave fronts. The sound field emitted by a uniformly moving monopole source is derived and the far-field radiation properties of the complex virtual source under consideration are incorporated in order to derive a closed-form expression for the loudspeaker driving signal. The results are illustrated via numerical simulations of the synthesis of the sound field of a sample moving complex virtual source.
Enhancement of interaural level differences improves sound localization in bimodal hearing
Authors: Francart Tom , Lenssen Anneke , Wouters Jan
Published: November 2011

Users of a cochlear implant together with a contralateral hearing aid—so-called bimodal listeners—have difficulties with localizing sound sources. This is mainly due to the distortion of interaural time and level difference cues (ITD and ILD), and limited ITD sensitivity. An algorithm is presented that enhances ILD cues. Horizontal plane sound-source localization performance of six bimodal listeners was evaluated in (1) a real sound field with their clinical devices, (2) in a virtual sound field, under direct computer control, and (3) in a virtual sound field with ILD enhancement. The results in the real sound field did not differ significantly from the results in the virtual field, and ILD enhancement improved localization performance by 4°–10° absolute error, relative to a mean absolute error of 28° in the condition without ILD enhancement.
A cross-language study of compensation in response to real-time formant perturbation
Authors: Mitsuya Takashi , MacDonald Ewen N. , Purcell David W. , Munhall Kevin G.
Published: November 2011

Past studies have shown that when formants are perturbed in real time, speakers spontaneously compensate for the perturbation by changing their formant frequencies in the opposite direction to the perturbation. Further, the pattern of these results suggests that the processing of auditory feedback error operates at a purely acoustic level. This hypothesis was tested by comparing the response of three language groups to real-time formant perturbations, (1) native English speakers producing an English vowel /ε/, (2) native Japanese speakers producing a Japanese vowel (/e⊤/), and (3) native Japanese speakers learning English, producing /ε/. All three groups showed similar production patterns when F1 was decreased; however, when F1 was increased, the Japanese groups did not compensate as much as the native English speakers. Due to this asymmetry, the hypothesis that the compensatory production for formant perturbation operates at a purely acoustic level was rejected. Rather, some level of phonological processing influences the feedback processing behavior.
A re-evaluation of auditory filter shape in delphinid odontocetes: Evidence of constant-bandwidth filters
Authors: Lemonds D. W. , Kloepper L. N. , Nachtigall P. E. , Au W. W. L. , Vlachos S. A. , Branstetter B. K.
Published: November 2011

The auditory filter shape of delphinid odontocetes was previously considered to be typically mammalian constant-quality in which filter bandwidths increase proportionally with frequency. Recent studies with porpoises demonstrate constant-bandwidth portions of the auditory filter. The critical ratios for a bottlenose dolphin were measured between 40 and 120 kHz by behaviorally determining the subject’s ability to detect pure tones in the presence of white noise. Critical ratios as a function of frequency were constant, indicating the auditory filter acts as a constant-bandwidth system in this frequency range. Re-analysis of past studies supports these findings, and suggests the delphinid auditory system is best characterized as a constant-Q system below 40 kHz and a constant-bandwidth-like system between 40 kHz and 120 kHz before returning to a constant Q pattern at the highest frequencies.
Optimum array design to maximize Fisher information for bearing estimation
Authors: Tuladhar Saurav R. , Buck John R.
Published: November 2011

Source bearing estimation is a common application of linear sensor arrays. The Cramer–Rao bound (CRB) sets a lower bound on the achievable mean square error (MSE) of any unbiased bearing estimate. In the spatially white noise case, the CRB is minimized by placing half of the sensors at each end of the array. However, many realistic ocean environments have a mixture of both white noise and spatially correlated noise. In shallow water environments, the correlated ambient noise can be modeled as cylindrically isotropic. This research designs a fixed aperture linear array to maximize the bearing Fisher information (FI) under these noise conditions. The FI is the inverse of the CRB, so maximizing the FI minimizes the CRB. The elements of the optimum array are located closer to the array ends than uniform spacing, but are not as extreme as in the white noise case. The optimum array results from a trade off between maximizing the array bearing sensitivity and minimizing output noise power variation over the bearing. Depending on the source bearing, the resulting improvement in MSE performance of the optimized array over a uniform array is equivalent to a gain of 2–5 dB in input signal-to-noise ratio.
The redundancy of phonemes in sentential context
Authors: Stilp Christian E.
Published: November 2011

Printed English is highly redundant as demonstrated by readers’ facility at guessing which letter comes next in text. However, such findings have been generalized to perception of connected speech without any direct assessment of phonemic redundancy. Here, participants guessed which phoneme or printed character came next throughout each of four unrelated sentences. Phonemes displayed significantly lower redundancy than letters, and possible contributing factors (task difficulty, experience, context) are discussed. Of three models tested, phonemic guessing was best approximated by word-initial and transitional probabilities between phonemes. Implications for information-theoretic accounts of speech perception are considered.
Forced vibrations of a bubble in a liquid-filled elastic vessel
Authors: Martynov Sergey , Kostson Erik , Saffari Nader , Stride Eleanor
Published: November 2011

There is increasing demand for accurate characterization of the in vivo behavior of microbubble agents used for ultrasound imaging and therapy. This study examines bubble-vessel interaction, in particular the propagation of disturbances along the vessel wall. Finite element simulations of a 3 μm radius microbubble suspended in a viscous liquid and enclosed in a 4 μm radius elastic vessel were performed, and the results compared with existing analytical results for wave propagation in elastic liquid-filled tubes. The vessel wall was shown to have a significant effect upon the amplitude of bubble oscillation and hence acoustic radiation from it, as well as distension of the vessel wall. It was found that the most important factor was the ratio of the excitation frequency to the natural “ring” frequency of the vessel which in turn depends upon its dimensions and mechanical properties. As this ratio increases, the motion of the vessel wall becomes increasingly localized to the site of the bubble. It was also shown that the validity of the results obtained using the applied model of vessel elasticity is limited to frequencies below the ring frequency, and this should be taken into account in the development of protocols for ultrasound safety and/or therapeutic procedures.
Domain Dynamics During Ferroelectric Switching
Authors: Nelson Christopher T. , Gao Peng , Jokisaari Jacob R. , Heikes Colin , Adamo Carolina , Melville Alexander , Baek Seung-Hyub , Folkman Chad M. , Winchester Benjamin , Gu Yijia , Liu Yuanming , Zhang Kui , Wang Enge , Li Jiangyu , Chen Long-Qing , Eom Chang-Beom , Schlom Darrell G. , Pan Xiaoqing
Published: November 2011

The role of defects and interfaces on switching in ferroelectric materials is observed with high-resolution microscopy.
To Close the Gap
The Next Convergence
The Future of Economic Growth in a Multispeed World

by Michael Spence

Farrar, Straus and Giroux, New York, 2011. 312 pp. $27, £17.99. ISBN 9780374159757.
Authors: Jones Charles I.
Published: November 2011

After weighing explanations for the high growth rates experienced in the developing world over the past half-century, Spence turns to consider the global economy over the next 50 years.
Antioxidant Strategies to Tolerate Antibiotics
Authors: Belenky Peter , Collins James J.
Published: November 2011

Bacteria use two convergent strategies to combat toxic reactive oxygen species produced in response to antibiotic treatment.
One Atom Makes All the Difference
Authors: Ramaswamy S.
Published: November 2011

The interstitial atom in the nitrogenase FeMo cofactor cluster is carbon, not nitrogen as previously surmised.
Steven P. Jobs (1955–2011)
Authors: Misa Thomas J.
Published: November 2011

A brash, innovative, and intuitive thinker spurred radical technological changes that reshaped the cultural and economic landscape.
Dreams of a Lithium Empire
Authors: Friedman-Rudovsky Jean
Published: November 2011

Bolivia is betting that a former nuclear engineer, Guillaume Roelants, will develop a new extraction process for the world's largest lithium reserve.
Turning Over a New Leaf
Authors: Service Robert F.
Published: November 2011

Artificial-photosynthesis researchers dream of using sunlight's energy to generate chemical fuels. Despite progress, the approach must become more efficient and cheaper to make an impact on where the world gets its fuel.
Chaperone-Mediated Autophagy Is Required for Tumor Growth
Authors: Kon Maria , Kiffin Roberta , Koga Hiroshi , Chapochnick Javier , Macian Fernando , Varticovski Lyuba , Cuervo Ana Maria
Published: November 2011

Cancer cells depend on chaperone-mediated autophagy for growth, revealing a new target for preventing tumorigenesis and inducing tumor regression.
Another Reason to Exercise
Authors: Hong David S.
Published: November 2011

Fat cells promote ovarian cancer.
The Skeleton Key for Intracellular Pathogens: Nanoparticles and Pulmonary Vaccination
Authors: Nyendak Melissa
Published: November 2011

A nanoparticle-linked antigen induces cytotoxic T cell responses and protective immunity against influenza in mice.
Brain Stimulation and Decision-Making
Authors: Wang Wei
Published: November 2011

Experiments probe the effect of deep brain stimulation on the neural circuitry for decision-making and impulsive behavioral control.
Emergence of Carbapenem-Resistant Non-baumannii Species of Acinetobacter Harboring a
bla
OXA-51
-Like Gene That Is Intrinsic to A. baumannii
Authors: Lee Yi-Tzu , Kuo Shu-Chen , Chiang Mei-Chun , Yang Su-Pen , Chen Chien-Pei , Chen Te-Li , Fung Chang-Phone
Published: November 2011

The
bla
OXA-51
-like gene, originally intrinsic to
Acinetobacter baumannii
, had been detected in two clones of
Acinetobacter nosocomialis
and one clone of
Acinetobacter
genomic species “Close to 13TU.” These
bla
OXA-51
-like genes, all preceded by IS
Aba1
, were located on plasmids that might have originated with
A. baumannii
. The plasmid-borne IS
Aba1
--
bla
OXA-51
-like confers a high level of carbapenem resistance and affects the accuracy of using
bla
OXA-51
-like detection as a tool for differentiating
A. baumannii
from other
Acinetobacter
species.
Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods
Authors: Castanheira Mariana , Duncanson Frederick P. , Diekema Daniel J. , Guarro Josep , Jones Ronald N. , Pfaller Michael A.
Published: November 2011

Fusarium
(
n
= 67) and
Scedosporium
(
n
= 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of
Fusarium
(4 isolates unspeciated) and 28
Scedosporium apiospermum
, 7
Scedosporium aurantiacum
, and 28
Scedosporium prolificans
species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC
90
values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for
Fusarium
of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the
Scedosporium
spp. tested. The E1210 MEC
90
was 0.12 μg/ml for
S. apiospermum
, but 1 to >8 μg/ml for other tested agents. Against
S. aurantiacum
, the MEC
50
for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against
S. prolificans
, the MEC
90
for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and
F. oxysporum
species complex (SC) (60%), posaconazole and
S. aurantiacum
(85.7%), and voriconazole and
S. aurantiacum
(85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of
Fusarium
spp. and
Scedosporium
spp. Furthermore,
in vitro
susceptibility testing of E1210 against isolates of
Fusarium
and
Scedosporium
may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.
Effects of Melaleuca alternifolia (Tea Tree) Essential Oil and the Major Monoterpene Component Terpinen-4-ol on the Development of Single- and Multistep Antibiotic Resistance and Antimicrobial Susceptibility
Authors: Hammer Katherine A. , Carson Christine F. , Riley Thomas V.
Published: November 2011

This study examined the effect of subinhibitory
Melaleuca alternifolia
(tea tree) essential oil on the development of antibiotic resistance in
Staphylococcus aureus
and
Escherichia coli
. Frequencies of single-step antibiotic-resistant mutants were determined by inoculating bacteria cultured with or without subinhibitory tea tree oil onto agar containing 2 to 8 times the MIC of each antibiotic and with or without tea tree oil. Whereas most differences in resistance frequencies were relatively minor, the combination of kanamycin and tea tree oil yielded approximately 10-fold fewer resistant
E. coli
mutants than kanamycin alone. The development of multistep antibiotic resistance in the presence of tea tree oil or terpinen-4-ol was examined by culturing
S. aureus
and
E. coli
isolates daily with antibiotic alone, antibiotic with tea tree oil, and antibiotic with terpinen-4-ol for 6 days. Median MICs for each antibiotic alone increased 4- to 16-fold by day 6. Subinhibitory tea tree oil or terpinen-4-ol did not greatly alter results, with day 6 median MICs being either the same as or one concentration different from those for antibiotic alone. For tea tree oil and terpinen-4-ol alone, day 6 median MICs had increased 4-fold for
S. aureus
(
n
= 18) and 2-fold for
E. coli
(
n
= 18) from baseline values. Lastly, few significant changes in antimicrobial susceptibility were seen for
S. aureus
and
S. epidermidis
isolates that had been serially subcultured 14 to 22 times with subinhibitory terpinen-4-ol. Overall, these data indicate that tea tree oil and terpinen-4-ol have little impact on the development of antimicrobial resistance and susceptibility.
Pathoadaptive Conditional Regulation of the Type VI Secretion System in Vibrio cholerae O1 Strains
Authors: Ishikawa Takahiko , Sabharwal Dharmesh , Bröms Jeanette , Milton Debra L. , Sjöstedt Anders , Uhlin Bernt Eric , Wai Sun Nyunt
Published: November 2011

The most recently discovered secretion pathway in Gram-negative bacteria, the type VI secretion system (T6SS), is present in many species and is considered important for the survival of non-O1 non-O139
Vibrio cholerae
in aquatic environments. Until now, it was not known whether there is a functionally active T6SS in wild-type
V. cholerae
O1 strains, the cause of cholera disease in humans. Here, we demonstrate the presence of a functionally active T6SS in wild-type
V. cholerae
O1 strains, as evidenced by the secretion of the T6SS substrate Hcp, which required several gene products encoded within the putative
vas
gene cluster. Our analyses showed that the T6SS of wild-type
V. cholerae
O1 strain A1552 was functionally activated when the bacteria were grown under high-osmolarity conditions. The T6SS was also active when the bacteria were grown under low temperature (23°C), suggesting that the system may be important for the survival of the bacterium in the environment. A test of the interbacterial virulence of
V. cholerae
strain A1552 against an
Escherichia coli
K-12 strain showed that it was strongly enhanced under high osmolarity and that it depended on the
hcp
genes. Interestingly, we found that the newly recognized osmoregulatory protein OscR plays a role in the regulation of T6SS gene expression and secretion of Hcp from
V. cholerae
O1 strains.
RrgB321, a Fusion Protein of the Three Variants of the Pneumococcal Pilus Backbone RrgB, Is ProtectiveIn Vivoand Elicits Opsonic Antibodies
Authors: Harfouche Carole , Filippini Sara , Gianfaldoni Claudia , Ruggiero Paolo , Moschioni Monica , Maccari Silvia , Pancotto Laura , Arcidiacono Letizia , Galletti Bruno , Censini Stefano , Mori Elena , Giuliani Marzia , Facciotti Claudia , Cartocci Elena , Savino Silvana , Doro Francesco , Pallaoro Michele , Nocadello Salvatore , Mancuso Giuseppe , Haston Mitch , Goldblatt David , Barocchi Michèle A. , Pizza Mariagrazia , Rappuoli Rino , Masignani Vega
Published: November 2011

Streptococcus pneumoniaepilus 1 is present in 30 to 50% of invasive disease-causing strains and is composed of three subunits: the adhesin RrgA, the major backbone subunit RrgB, and the minor ancillary protein RrgC. RrgB exists in three distinct genetic variants and, when used to immunize mice, induces an immune response specific for each variant. To generate an antigen able to protect against the infection caused by all pilus-positiveS. pneumoniaestrains, we engineered a fusion protein containing the three RrgB variants (RrgB321). RrgB321 elicited antibodies against proteins from organisms in the three clades and protected mice against challenge with piliated pneumococcal strains. RrgB321 antisera mediated complement-dependent opsonophagocytosis of piliated strains at levels comparable to those achieved with the PCV7 glycoconjugate vaccine. These results suggest that a vaccine composed of RrgB321 has the potential to cover 30% or more of all pneumococcal strains and support the inclusion of this fusion protein in a multicomponent vaccine againstS. pneumoniae.
Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus
Authors: Li Xianping , Gao Meihua , Han Xuelin , Tao Sha , Zheng Dongyu , Cheng Ying , Yu Rentao , Han Gaige , Schmidt Martina , Han Li
Published: November 2011

Aspergillus fumigatusis the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases onA. fumigatusvirulence is rather limited. In this study, disruption of thepldgene encoding phospholipase D (PLD), an important member of the phospholipase protein family inA. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity ofA. fumigatus. Thepldgene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization ofA. fumigatusinto A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 μM phosphatidic acid, the PLD product. Indeed, complementation ofpldrestored the PLD activity and internalization capacity ofA. fumigatus. Phagocytosis ofA. fumigatusconidia by J774 macrophages was not affected by the absence of thepldgene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization ofA. fumigatusinto A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of thepldgene attenuated the virulence ofA. fumigatusin mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD ofA. fumigatusregulates its internalization into lung epithelial cells and may represent an important virulence factor forA. fumigatusinfection.
Oral Infection with Signature-Tagged Listeria monocytogenes Reveals Organ-Specific Growth and Dissemination Routes in Guinea Pigs
Authors: Melton-Witt Jody A. , Rafelski Susanne M. , Portnoy Daniel A. , Bakardjiev Anna I.
Published: November 2011

Listeria monocytogenescauses a serious food-borne disease due to its ability to spread from the intestine to other organs, a process that is poorly understood. In this study we used 20 signature-tagged wild-type clones ofL. monocytogenesin guinea pigs in combination with extensive quantitative data analysis to gain insight into extraintestinal dissemination. We show thatL. monocytogenescolonized the liver in all asymptomatic animals. Spread to the liver occurred as early as 4 h after ingestion via a direct pathway from the intestine to the liver. This direct pathway contributed significantly to the bacterial load in the liver and was followed by a second wave of dissemination via the mesenteric lymph nodes (indirect pathway). Furthermore, bacteria were eliminated in the liver, whereas small intestinal villi provided a niche for bacterial replication, indicating organ-specific differences in net bacterial growth. Bacteria were shed back from intestinal villi into the small intestinal lumen and reinfected the Peyer's patches. Together, these results support a novel dissemination model whereL. monocytogenesreplicates in intestinal villi, is shed into the lumen, and reinfects intestinal immune cells that traffic to liver and mesenteric lymph nodes, a process that occurs even during asymptomatic colonization.
In Vitro
Assembly of Virus-Like Particles of a Gammaretrovirus, the Murine Leukemia Virus XMRV
Authors: Hadravová Romana , de Marco Alex , Ulbrich Pavel , Štokrová Jitka , Doležal Michal , Pichová Iva , Ruml Tomáš , Briggs John A. G. , Rumlová Michaela
Published: November 2011

Immature retroviral particles are assembled by self-association of the structural polyprotein precursor Gag. During maturation the Gag polyprotein is proteolytically cleaved, yielding mature structural proteins, matrix (MA), capsid (CA), and nucleocapsid (NC), that reassemble into a mature viral particle. Proteolytic cleavage causes the N terminus of CA to fold back to form a β-hairpin, anchored by an internal salt bridge between the N-terminal proline and the inner aspartate. Using an
in vitro
assembly system of capsid-nucleocapsid protein (CANC), we studied the formation of virus-like particles (VLP) of a gammaretrovirus, the xenotropic murine leukemia virus (MLV)-related virus (XMRV). We show here that, unlike other retroviruses, XMRV CA and CANC do not assemble tubular particles characteristic of mature assembly. The prevention of β-hairpin formation by the deletion of either the N-terminal proline or 10 initial amino acids enabled the assembly of ΔProCANC or Δ10CANC into immature-like spherical particles. Detailed three-dimensional (3D) structural analysis of these particles revealed that below a disordered N-terminal CA layer, the C terminus of CA assembles a typical immature lattice, which is linked by rod-like densities with the RNP.
Mapping physicians' admission diagnoses to structured concepts towards fully automatic calculation of acute physiology and chronic health evaluation score
Authors: Chandra Subhash , Kashyap Rahul , Trillo-Alvarez Cesar A , Tsapenko Mykola , Yilmaz Murat , Hanson Andrew C , Pickering Brian W , Gajic Ognjen , Herasevich Vitaly
Published: November 2011

Objective

Acute Physiology and Chronic Health Evaluation (APACHE) is most widely used as a mortality prediction score in US intensive care units (ICUs), but its calculation is onerous. The authors aimed to develop and validate automatic mapping of physicians' admission diagnoses to structured concepts for automated APACHE IV calculation.

Methods

This retrospective study was conducted in medical ICUs of a tertiary healthcare and academic centre. Boolean-logic text searches were used to map admission diagnoses, and these were compared with conventional APACHE database entry by bedside nurses and a gold-standard physician chart review. The primary outcome was APACHE IV predicted hospital mortality. The tool was developed in a larger cohort of ICU patients.

Results

In a derivation cohort of 192 consecutive critically ill patients, the diagnosis coefficient coded by three different methods had a positive correlation, highest between manual and gold standard (r2=0.95; mean square error (MSE)=0.040) and least between manual and automatic tool (r2=0.88; MSE=0.066). The automatic tool had an area under the curve (95% CI) value of 0.82 (0.74 to 0.90) which was similar to the physician gold standard, 0.83 (0.75 to 0.91) and standard manual entry, 0.81 (0.73 to 0.89). The Hosmer–Lemeshow goodness-of-fit test demonstrated good calibration of automatically calculated APACHE IV score (χ2=6.46; p=0.6). The automatic tool demonstrated excellent discrimination with an area under the curve value of 0.87 (95% CI 0.83 to 0.92) and good calibration (p=0.58) in the validation cohort of 593 patients.

Conclusion

A Boolean-logic text search is an efficient alternative to manual database entry for mapping of ICU admission diagnosis to structured APACHE IV concepts.