bluuebunny/crossref_metadata_2025 huggingface dataset:
Local silencing controls the oxidative stress response and the multidrug resistance in Candida glabrata
Authors: Orta‐Zavalza Emmanuel , Guerrero‐Serrano Gehenna , Gutiérrez‐Escobedo Guadalupe , Cañas‐Villamar Israel , Juárez‐Cepeda Jacqueline , Castaño Irene , De Las Peñas Alejandro
Published: May 2013

In Candida glabrata, the sirtuins Sir2 and Hst1 control the expression of a wide number of genes including adhesins required for host colonization and niacin transporters needed for growth. Given that these sirtuins can be inactivated during infection, we asked if their inhibition could modify the response of C. glabrata to other stressful conditions. Here, we found that deletion of HST1 decreases susceptibility of C. glabrata to fluconazole and hydrogen peroxide. The transcription factor Pdr1 and the ABC transporter Cdr1 mediated the fluconazole resistance phenotype of the hst1Δ cells, whereas the transcriptional activator Msn4 and the catalase Cta1 are necessary to provide oxidative stress resistance. We show that the transcription factor Sum1 interacts with Hst1 and participate in the regulation of these genes. Interestingly, even though C. glabrata and Saccharomyces cerevisiae are closely related phylogenetically, deletion of HST1 decreased susceptibility to fluconazole and hydrogen peroxide only in C. glabrata but not in S. cerevisiae, indicating a different transcriptional control by two similar sirtuins. Our findings suggest that Hst1 acts as a regulator of stress resistance associated‐genes.
A novel RNA polymerase‐binding protein controlling genes involved in spore germination in Bacillus subtilis
Authors: Traag Bjorn A. , Ramirez‐Peralta Arturo , Wang Erickson Anna F. , Setlow Peter , Losick Richard
Published: May 2013

A growing class of proteins regulates transcription through interaction with DNA‐dependent RNA polymerase. Here we report that a recently identified, highly conserved sporulation gene ylyA encodes a novel RNA polymerase‐binding protein that influences the expression of genes under the control of the late‐acting, sporulation sigma factor σG in Bacillus subtilis. Spores from a ylyA mutant exhibited defects in germination corresponding to changes in the levels of membrane receptors for spore germinants and a protein channel governing the release of dipicolinic acid and hydration of the spore core during germination. Purified YlyA interacted with RNA polymerase and stimulated transcription from promoters dependent on σG but not promoters dependent on the housekeeping sigma factor σA. YlyA is a previously unrecognized RNA polymerase‐binding protein that is dedicated to modulating the expression of genes involved in spore germination.
Superoxide poisons mononuclear iron enzymes by causing mismetallation
Authors: Gu Mianzhi , Imlay James A.
Published: May 2013

Superoxide (O2−) is a primary agent of intracellular oxidative stress. Genetic studies in many organisms have confirmed that excess O2− disrupts metabolism, but to date only a small family of [4Fe‐4S] dehydratases have been identified as direct targets. This investigation reveals that in Escherichia coli O2− also poisons a broader cohort of non‐redox enzymes that employ ferrous iron atoms as catalytic cofactors. These enzymes were inactivated by O2− both in vitro and in vivo. Although the enzymes are known targets of hydrogen peroxide, the outcome with O2− differs substantially. When purified enzymes were damaged by O2− in vitro, activity could be completely restored by iron addition, indicating that the O2− treatment generated an apoprotein without damaging the protein polypeptide. Superoxide stress inside cells caused the progressive mismetallation of these enzymes with zinc, which confers little activity. When O2− stress was terminated, cells gradually restored activity by extracting zinc from the proteins. The overloading of cells with zinc caused mismetallation even without O2− stress. These results support a model in which O2− repeatedly excises iron from these enzymes, allowing zinc to compete with iron for remetallation of their apoprotein forms. This action substantially expands the physiological imprint of O2− stress.
Both human ferredoxins equally efficiently rescue ferredoxin deficiency in Trypanosoma brucei
Authors: Changmai Piya , Horáková Eva , Long Shaojun , Černotíková‐Stříbrná Eva , McDonald Lindsay M. , Bontempi Esteban J. , Lukeš Julius
Published: May 2013

Ferredoxins are highly conserved proteins that function universally as electron transporters. They not only require Fe‐S clusters for their own activity, but are also involved in Fe‐S formation itself. We identified two homologues of ferredoxin in the genome of the parasitic protist Trypanosoma brucei and named them TbFdxA and TbFdxB. TbFdxA protein, which is homologous to other eukaryotic mitochondrial ferredoxins, is essential in both the procyclic (= insect‐transmitted) and bloodstream (mammalian) stage, but is more abundant in the active mitochondrion of the former stage. Depletion of TbFdxA caused disruption of Fe‐S cluster biogenesis and lowered the level of intracellular haem. However, TbFdxB, which is present exclusively within kinetoplastid flagellates, was non‐essential for the procyclic stage, and double knock‐down with TbFdxA showed this was not due to functional redundancy between the two homologues. Heterologous expressions of human orthologues HsFdx1 and HsFdx2 fully rescued the growth and Fe‐S‐dependent enzymatic activities of TbFdxA knock‐down. In both cases, the genuine human import signals allowed efficient import into the T. brucei mitochondrion. Given the huge evolutionary distance between trypanosomes and humans, ferredoxins clearly have ancestral and highly conserved function in eukaryotes and both human orthologues have retained the capacity to participate in Fe‐S cluster assembly.
Transgenic resistance to Bamboo mosaic virus by expression of interfering satellite RNA
Authors: Lin Kuan‐Yu , Hsu Yau‐Heiu , Chen Hsin‐Chuan , Lin Na‐Sheng
Published: May 2013

Plant genetic engineering has broadened the options for plant virus resistance and is mostly based on pathogen‐derived resistance. Previously, we have shown that interfering satellite RNA (satRNA) of Bamboo mosaic virus (satBaMV) greatly reduces Bamboo mosaic virus (BaMV) accumulation and BaMV‐induced symptoms in co‐inoculated plants. Here, we generated a nonviral source of virus‐resistant transgenic Nicotiana benthamiana and Arabidopsis thaliana by introducing interfering satBaMV. Asymptomatic transgenic N. benthamiana lines were highly resistant to BaMV virion and viral RNA infection, and the expression of the transgene BSL6 was higher in asymptomatic than mildly symptomatic lines. In addition, BaMV‐ and satBaMV‐specific small RNAs were detectable only after BaMV challenge, and their levels were associated with genomic viral RNA or satRNA levels. By transcriptomic analysis, the salicylic acid (SA) signalling pathway was not induced in satBaMV transgenic A. thaliana in mock conditions, suggesting that two major antiviral mechanisms, RNA silencing and SA‐mediated resistance, are not involved directly in transgenic satBaMV‐mediated BaMV interference. In contrast, resistance is associated with the level of the interfering satBaMV transgene. We propose satBaMV‐mediated BaMV interference in transgenic plants by competition for replicase with BaMV.
Brain haemosiderin in older people: pathological evidence for an ischaemic origin of magnetic resonance imaging (MRI) microbleeds
Authors: Janaway B. M. , Simpson J. E. , Hoggard N. , Highley J. R. , Forster G. , Drew D. , Gebril O. H. , Matthews F. E. , Brayne C. , Wharton S. B. , Ince P. G. ,   MRC Cognitive Function and Ageing Neuropathology Study
Published: May 2013

Introduction

Magnetic resonance imaging (MRI) cerebral microbleeds (CMB) arise from ferromagnetic haemosiderin iron assumed to derive from extravasation of erythrocytes. Light microscopy of ageing brain frequently reveals foci of haemosiderin from single crystalloids to larger, predominantly perivascular, aggregates. The pathological and radiological relationship between these findings is not resolved.

Methods

Haemosiderin deposition and vascular pathology in the putamen were quantified in 200 brains donated to the population‐representative Medical Research Council Cognitive Function and Ageing Study. Molecular markers of gliosis and tissue integrity were assessed by immunohistochemistry in brains with highest (n = 20) and lowest (n = 20) levels of putamen haemosiderin. The association between haemosiderin counts and degenerative and vascular brain pathology, clinical data, and the haemochromatosis (HFE) gene H63D genotype were analysed. The frequency of MRI CMB in 10 cases with highest and lowest burden of putamen haemosiderin, was compared using post mortem 3T MRI.

Results

Greater putamen haemosiderin was significantly associated with putaminal indices of small vessel ischaemia (microinfarcts, P < 0.05; arteriolosclerosis, P < 0.05; perivascular attenuation, P < 0.001) and with lacunes in any brain region (P < 0.023) but not large vessel disease, or whole brain measures of neurodegenerative pathology. Higher levels of putamen haemosiderin correlated with more CMB (P < 0.003).

Conclusions

The MRI‐CMB concept should take account of brain iron homeostasis, and small vessel ischaemic change in later life, rather than only as a marker for minor episodes of cerebrovascular extravasation. These data are of clinical relevance, suggesting that basal ganglia MRI microbleeds may be a surrogate for ischaemic small vessel disease rather than exclusively a haemorrhagic diathesis.
Maternal nutrition: Building foundations of long‐term good health
Authors: Salisbury C. , Robertson C.
Published: May 2013

We know that improving maternal and infant nutrition prior to conception and up to 2 years is the most fundamental and impactful way to positively affect the long‐term health of the population in both the developing and developed world. Evidence demonstrates that suboptimal maternal nutrition impairs fetal growth and development and can lead to cognitive impairment and an increased risk of non‐communicable disease in adult life. Improving maternal diet and nutritional status will be a significant and cost‐effective step in tackling both malnutrition and chronic disease globally. However, this long‐term goal cannot be achieved without general recognition and meaningful commitment on both a national and international level to implement long‐term strategies to support all women of childbearing age to make healthy diet and lifestyle choices before, during and after pregnancy.
Support interventions for caregivers of physically disabled adults: A systematic review
Authors: Lawang Wannarat , Horey Dell , Blackford Jeanine , Sunsern Rachanee , Riewpaiboon Wachara
Published: May 2013

In developing countries family caregivers are an important community‐based resource who provide care for physically disabled adults. Substantial caregiving commitment is known to adversely affect caregiver health and thereby their capacity to provide ongoing care. This systematic review focused on support interventions for caregivers using Thailand as an example. From 1964 to 2011 international and Thai electronic databases and relevant grey literature were searched. Six English papers and 34 Thai papers published between 1990 and 2010 were found. The Critical Appraisal Skills Programme (CASP) tool was modified to appraise methodological quality. All nurse‐led interventions mainly focused on improving caregiving capacity; nearly half considered caregiver health. Only 15 interventions were community‐based. Despite variable research quality all studies showed benefits for caregivers, care recipients, and healthcare services. In developing countries without healthy caregivers physically disabled adults would not receive care. There is an urgent need for further investment in community‐based research to develop effective interventions designed to promote caregiver health and help them maintain their role.
Specific‐gene studies of evolutionary mechanisms in an age of genome‐wide surveying
Authors: Watt Ward B.
Published: May 2013

The molecular tools of genomics have great power to reveal patterns of genetic difference within or among species, but must be complemented by the mechanistic study of the genetic variants found if these variants’ evolutionary meaning is to be well understood. Central to this purpose is knowledge of the organisms’ genotype–phenotype–environment interactions, which embody biological adaptation and constraint and thus drive natural selection. The history of this approach is briefly reviewed. Strategies embracing the complementarity of genomics and specific‐gene studies in evolution are considered. Implementation of these strategies, and examples showing their feasibility and power, are discussed. Initial generalizations emphasize: (1) reproducibility of adaptive mechanisms; (2) evolutionary co‐importance of variation in protein sequences and expression; (3) refinement of rudimentary molecular functions as an origin of evolutionary innovations; (4) identification of specific‐gene mechanisms as underpinnings of genomic or quantitative genetic variation; and (5) multiple forms of adaptive or constraining epistasis among genes. Progress along these lines will advance understanding of evolution and support its use in addressing urgent medical and environmental applications.
Low phosphorus status might contribute to the onset of obesity
Authors: Obeid O. A.
Published: May 2013

Overweight and obesity are becoming global health problems. Although genetics certainly plays a role, weight gain is ultimately the result of a failure in the balance between energy expenditure and energy intake. Obesity during the past few decades was paralleled with several changes in dietary habits favouring low phosphorus consumption. This is believed to compromise adenosine triphosphate (ATP) production that is involved in the regulation of energy metabolism. Ingestion of high‐carbohydrate–low phosphorus food is known to increase insulin release, to simultaneously stimulate peripheral uptake of phosphorus and the phosphorylation of many compounds. This creates a competition for phosphorus that compromises its availability for ATP production, possibly translated into low diet‐induced thermogenesis. Moreover, reduced hepatic ATP production is believed to be transmitted through neural afferents to the central nervous system, resulting in an increase in food intake. On the other hand, the positive relation between phosphorus and red blood cell 2,3‐diphosphoglycerate, which reduces oxygen affinity to haemoglobin, would be expected to reduce the capacity for physical activity. In line with that, plasma phosphorus status was reported to be inversely related to body weight. Adequate intakes of phosphorus are thus potentially protective against rising obesity epidemic across the globe.
Impact of Cardiac Computed Tomography of the Interatrial Septum before Pulmonary Vein Isolation
Authors: KOBZA RICHARD , SCHOENENBERGER ANDREAS W. , CUCULI FLORIM , ZUBER MICHEL , AUF DER MAUR CHRISTOPH , BUHMANN RALF , RESINK THERESE J. , ERNE PAUL
Published: May 2013

Background

Multidetector computed tomography (MDCT) may be useful to identify patients with patent foramen ovale (PFO). The aim of this study was to analyze whether a MDCT performed before pulmonary vein isolation reliably detects a PFO that may be used for access to the left atrium.

Methods and Results

In 79 consecutive patients, who were referred for catheter ablation of symptomatic paroxysmal or persistent atrial fibrillation (AF), the presence of a PFO was explored by MDCT and transesophageal echocardiography (TEE). TEE was considered as the gold standard, and quality of TEE was good in all patients. In 16 patients (20.3%), MDCT could not be used for analysis because of artifacts, mainly because of AF. On TEE, a PFO was found in 15 (23.8%) of the 63 patients with usable MDCT. MDCT detected six PFO of which four were present on TEE. This corresponded to a sensitivity of 26.7%, a specificity of 95.8%, a negative predictive value of 80.7%, and a positive predictive value of 66.7%. The receiver operating characteristics curve of MDCT for the detection of PFO was 0.613 (95% confidence interval 0.493–0.732).

Conclusions

MDCT may detect a PFO before pulmonary isolation. However, presence of AF may lead to artifacts on MDCT impeding a meaningful analysis. Furthermore, in this study sensitivity and positive predictive value of MDCT were low and therefore MDCT was not a reliable screening tool for detection of PFO.
Decision making and action implementation: Evidence for an early visually triggered motor activation specific to potential actions
Authors: Tandonnet Christophe , Garry Michael I. , Summers Jeffery J.
Published: May 2013

To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential‐sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no‐go and between‐hand choice tasks by transcranial magnetic stimulation of the motor cortex (single‐ or paired‐pulse TMS; 3‐ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to‐be‐produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race‐like models with continuous transmission between decision making and action implementation.
Examining Latino Support for Descriptive Representation: The Role of Identity and Discrimination
Authors: Wallace Sophia J.
Published: May 2013

Objectives

To determine the role of linked fate, cultural factors, and experiences with discrimination on support for descriptive representation among Latinos.

Methods

Utilizing data from the Latino National Survey (2006) and ordered logistic regression this article analyzes the impact of Latino‐linked fate, cultural factors, and personal and group experiences with discrimination on desire for Latino representation.

Results

A higher sense of attachment to Latino‐linked fate and Spanish results in a greater desire for Latino representatives. Similarly, Latinos who believed Latinos suffered from group discrimination were in greater support of Latino representatives.

Conclusions

By examining descriptive representation from the perspective of how Latinos feel, this investigation improves our understanding of how attachment to a linked fate, language, and experiences with discrimination work to influence support for Latino representatives.
Increased incidence of herpes zoster in the setting of cytomegalovirus preemptive therapy after kidney transplantation
Authors: Ko G.B. , Kim T. , Kim S.‐H. , Choi S.‐H. , Kim Y.S. , Woo J.H. , Kim Y.H. , Park J.B. , Lee S.K. , Park S.‐K. , Park J.S. , Han D.J. , Lee S.‐O.
Published: May 2013

Background

Herpes zoster (HZ) is a common infectious disease after kidney transplantation (KT). The incidence of HZ may increase during cytomegalovirus (CMV) preemptive therapy. We therefore evaluated the incidence, risk factors, and clinical outcomes of HZ after KT, according to the type of CMV prophylaxis used.

Methods

We retrospectively established a cohort of KT recipients who underwent transplantation from June 2008 to May 2010. Patients were categorized into 3 groups according to CMV prophylaxis regimen: Group A (preemptive therapy), Group B (universal prophylaxis <3 months), and Group C (universal prophylaxis >3 months). The incidence rate of HZ was compared in each group, and risk factors for HZ were identified.

Results

The incidence rate of HZ was 46.6 (95% confidence interval [CI] 31.4–66.5) per 1000 person‐years. The incidence rate was higher in Group A than in Group C (80.0 vs. 13.0 per 1000 person‐years; P = 0.001). Median onset time of HZ after KT was shorter in Group A than in Group B (0.9 vs. 9.9 months; P < 0.001) and Group C (0.9 vs. 14.8 months; P = 0.008). Post‐herpetic neuralgia occurred in 7 patients (23%). No visceral involvement or death was related to HZ. By multivariate analysis, only female gender (corrected relative risk 1.59; 95% CI 1.09–2.00) was independently associated with HZ development.

Conclusions

In the setting of CMV preemptive therapy, a differentiated varicella zoster virus‐specific prophylaxis might be necessary for patients with HZ risk factors.
Uncertainty Reduction as a Measure of Cognitive Load in Sentence Comprehension
Authors: Frank Stefan L.
Published: May 2013

The entropy‐reduction hypothesis claims that the cognitive processing difficulty on a word in sentence context is determined by the word's effect on the uncertainty about the sentence. Here, this hypothesis is tested more thoroughly than has been done before, using a recurrent neural network for estimating entropy and self‐paced reading for obtaining measures of cognitive processing load. Results show a positive relation between reading time on a word and the reduction in entropy due to processing that word, supporting the entropy‐reduction hypothesis. Although this effect is independent from the effect of word surprisal, we find no evidence that these two measures correspond to cognitively distinct processes.
Optic chiasm B‐cell lymphoma in a 20‐month‐old Mastiff dog
Authors: Nagel Christine , Silver Tawni , Grahn Bruce
Published: May 2013

A 20‐month‐old intact female Mastiff dog presented for evaluation of acute blindness. Computed tomography confirmed a tumor involved the optic chiasm and optic nerves. A B‐cell lymphoma was confirmed with postmortem examinations. This case report documents a central nervous system neoplasm in a young dog.
Systematics of spiny‐backed treefrogs (Hylidae:Osteocephalus): anAmazonian puzzle
Authors: Jungfer Karl‐Heinz , Faivovich Julián , Padial José M. , Castroviejo‐Fisher Santiago , Lyra Mariana M. , V. M. Berneck Bianca , Iglesias Patricia P. , Kok Philippe J. R. , MacCulloch Ross D. , Rodrigues Miguel T. , Verdade Vanessa K. , Torres Gastello Claudia P. , Chaparro Juan Carlos , Valdujo Paula H. , Reichle Steffen , Moravec Jiří , Gvoždík Václav , Gagliardi‐Urrutia Giussepe , Ernst Raffael , De la Riva Ignacio , Means Donald Bruce , Lima Albertina P. , Señaris J. Celsa , Wheeler Ward C. , F. B. Haddad Célio
Published: May 2013

Spiny‐backed tree frogs of the genusOsteocephalusare conspicuous components of the tropical wet forests of theAmazon and theGuianaShield. Here, we revise the phylogenetic relationships ofOsteocephalusand its sister groupTepuihyla, using up to 6134 bp ofDNAsequences of nine mitochondrial and one nuclear gene for 338 specimens from eight countries and 218 localities, representing 89% of the 28 currently recognized nominal species. Our phylogenetic analyses reveal (i) the paraphyly ofOsteocephaluswith respect toTepuihyla, (ii) the placement of ‘Hyla’ warrenias sister toTepuihyla, (iii) the non‐monophyly of several currently recognized species withinOsteocephalusand (iv) the presence of low (<1%) and overlapping genetic distances among phenotypically well‐characterized nominal species (e.g.O. taurinusandO. oophagus) for the 16Sgene fragment used in amphibianDNAbarcoding. We propose a new taxonomy, securing the monophyly ofOsteocephalusandTepuihylaby rearranging and redefining the content of both genera and also erect a new genus for the sister group ofOsteocephalus. The colouration of newly metamorphosed individuals is proposed as a morphological synapomorphy forOsteocephalus. We recognize and define five monophyletic species groups withinOsteocephalus, synonymize three species ofOsteocephalus(O. germani,O. phasmatus andO. vilmae) and three species ofTepuihyla(T. celsae,T. galani andT. talbergae) and reallocate three species (Hyla helenaetoOsteocephalus,O. exophthalmustoTepuihylaandO. pearsonitoDryadercesgen. n.). Furthermore, we flag nine putative new species (an increase to 138% of the current diversity). We conclude that species numbers are largely underestimated, with most hidden diversity centred on widespread and polymorphic nominal species. The evolutionary origin of breeding strategies withinOsteocephalusis discussed in the light of this new phylogenetic hypothesis, and a novel type of amplexus (gular amplexus) is described.
Synergistic effects of combining morphological and molecular data in resolving the phylogenetic position of Semispathidium (Ciliophora, Haptoria) with description of Semispathidium breviarmatum sp. n. from tropical Africa
Authors: Vďačný Peter , Foissner Wilhelm
Published: May 2013

We describe a new species, Semispathidium breviarmatum sp. n., from tropical Africa and analyse its phylogenetic position within the subclass Haptoria, using live observation, various silver impregnation methods, SEM and the 18S rRNA gene. Semispathidium breviarmatum differs from its congeners by the much higher number of ciliary rows and by the shape and size of the extrusomes, that is, extrusive organelles that kill the prey. The phylogenetic position of Semispathidium is controversial due to its ‘hybrid’ morphology. Specifically, the cylindroidal body has a more or less discoidal oral bulge indicating an enchelyodonid origin, while the anteriorly curved somatic kineties suggest a spathidiid ancestor. In order to reconstruct the evolutionary history of Semispathidium and to unravel its affinity to other haptorians, we used synergistic effects of combining morphological and molecular data coming from 34 haptorian taxa. These analyses show that Semispathidium belongs to the order Spathidiida representing a basal lineage that is far from ordinary Spathidium species, but very likely related to Protospathidium and Enchelys. Any closer phylogenetic relationship between Semispathidium and Enchelyodon spp. is not recognized in morphological and molecular phylogenies and is consistently excluded by statistical tree topology tests.
A Novel Higher-Order Model-Free Adaptive Control for a Class of Discrete-Time SISO Nonlinear Systems
Authors: Jin Shangtai , Hou Zhongsheng , Chi Ronghu
Published: May 2013

In this work, a novel higher-order model-free adaptive control scheme is presented based on a dynamic linearization approach for a class of discrete-time single input and single output (SISO) nonlinear systems. The control scheme consists of an adaptive control law, a parameter estimation law, and a reset mechanism. The design and analysis of the proposed control approach depends merely on the measured input and output data of the controlled plant. The control performance is improved by using more information of control input and output error measured from previous sampling time instants. Rigorous mathematical analysis is developed to show the bounded input and bounded output (BIBO) stability of the closed-loop system. Two simulation comparisons show the effectiveness of the proposed control scheme.
Soft-Chemistry–Based Routes to Epitaxial α-Quartz Thin Films with Tunable Textures
Authors: Carretero-Genevrier A. , Gich M. , Picas L. , Gazquez J. , Drisko G. L. , Boissiere C. , Grosso D. , Rodriguez-Carvajal J. , Sanchez C.
Published: May 2013

Fabricating Quartz

Quartz is used industrially as an abrasive, as an inert glassy material, or for high-quality crystals in microelectronics. It is also valued for its piezoelectronic properties. However, it is hard to grow quartz as a patterned material or to integrate it into nanostructured devices.

Carretero-Genevrier
et al.

(p.
827
; see the Perspective by

Brinker and Clem

) have developed a method for preparing oriented epitaxial thin films of polycrystalline α-quartz on single-crystal silicon substrates using ambient pressure and temperatures below 1000°C. Different processing conditions can be used to fabricate quartz films with a variety of pore sizes or as a dense nonporous α-quartz film.
Phase Diagram of the Topological Superfluid
3
He Confined in a Nanoscale Slab Geometry
Authors: Levitin L. V. , Bennett R. G. , Casey A. , Cowan B. , Saunders J. , Drung D. , Schurig Th. , Parpia J. M.
Published: May 2013

Confined Helium

Helium-3 (
3
He) has superfluid phases closely related to topological insulators and topological superconductors. In geometrical confinement,
3
He is expected to support exotic excitations, but its phase diagram is largely unknown, as such measurements are experimentally challenging.

Levitin
et al.

(p.
841
) confine
3
He in a slab geometry of defined height and use nuclear magnetic resonance as a probe. As predicted by theory, the authors find that the confinement stabilizes some of the superfluid phases across a larger portion of the phase diagram with respect to the bulk and potentially provides a testbed for topological superfluidity.
3D Computational Imaging with Single-Pixel Detectors
Authors: Sun B. , Edgar M. P. , Bowman R. , Vittert L. E. , Welsh S. , Bowman A. , Padgett M. J.
Published: May 2013

Cheap Pix

Three-dimensional (3D) images can be captured by, for example, holographic imaging or stereoimaging techniques. To avoid using expensive optical components that are limited to specialized bands of wavelengths,

Sun
et al.

(p.
844
; see the Perspective by

Faccio and Leach

) projected pulses of randomly textured light onto an object. They were able to reconstruct an image of the 3D object by detecting the reflected light with several photodetectors without any need for lenses. The patterned light beams can thus in principle be substituted for light sources of any wavelength.
A Reconciled Estimate of Glacier Contributions to Sea Level Rise: 2003 to 2009
Authors: Gardner Alex S. , Moholdt Geir , Cogley J. Graham , Wouters Bert , Arendt Anthony A. , Wahr John , Berthier Etienne , Hock Regine , Pfeffer W. Tad , Kaser Georg , Ligtenberg Stefan R. M. , Bolch Tobias , Sharp Martin J. , Hagen Jon Ove , van den Broeke Michiel R. , Paul Frank
Published: May 2013

Melting Away

We assume the Greenland and Antarctica ice sheets are the main drivers of global sea-level rise, but how large is the contribution from other sources of glacial ice?

Gardner
et al.

(p.
852
) synthesize data from glacialogical inventories to find that glaciers in the Arctic, Canada, Alaska, coastal Greenland, the southern Andes, and high-mountain Asia contribute approximately as much melt water as the ice sheets themselves: 260 billion tons per year between 2003 and 2009, accounting for about 30% of the observed sea-level rise during that period.
Rationally Designed Complex, Hierarchical Microarchitectures
Authors: Noorduin Wim L. , Grinthal Alison , Mahadevan L. , Aizenberg Joanna
Published: May 2013

Falling Out

During simple precipitation, molecules fall out of solution from locations of highest concentration and, consequently, the shape of the precipitate will be dictated by its crystallization thermodynamics.

Noorduin
et al.

(p.
832
; see the Perspective by

Vlieg

) designed micrometer-scale structures by varying the reaction conditions for silica and carbonate precipitation in which precipitation changes the local concentration and acidity to alter the next stage of precipitation, thus controlling whether the solid phase grows toward or away from the bulk solution. The result is the ability to design and generate a variety of complex structures by simple reaction-diffusion processes.
Dual Molecular Signals Mediate the Bacterial Response to Outer-Membrane Stress
Authors: Lima Santiago , Guo Monica S. , Chaba Rachna , Gross Carol A. , Sauer Robert T.
Published: May 2013

Stress Inside Out

In Gram-negative bacteria, the integrity of the outer membrane is crucial for survival and is an important aspect of resistance to antibiotics. The biogenesis of the major components lipopolysaccharide (LPS) and outer-membrane protein (OMP) of the outer membrane begins in the cytoplasmic compartment, involves export across the inner membrane and transport through the periplasm, and finally requires active insertion into the outer membrane by specialized assembly machines.

Lima
et al.

(p.
837
) supply results for a model in which serious defects in LPS biogenesis also create problems for OMP biogenesis, thereby producing the two signals needed to activate the σ
E
stress response pathway.
Quartz on Silicon
Authors: Brinker C. Jeffrey , Clem Paul G.
Published: May 2013

The integration of quartz with silicon may provide a route to fabricate advanced piezoelectric devices.

[Also see Research Article by

Carretero-Genevrier
et al.

]
Response to Comment on "Stress in Puberty Unmasks Latent Neuropathological Consequences of Prenatal Immune Activation in Mice"
Authors: Giovanoli Sandra , Meyer Urs
Published: May 2013

Lazic criticizes the statistical analyses used to support the conclusions in our mouse model. His theory-biased criticism is disproportionate in view of the robustness of our findings (even if different statistical methods are applied) and falls short in explaining the postpubertal onset of effects.
Ghost Imaging in Three Dimensions
Authors: Faccio Daniele , Leach Jonathan
Published: May 2013

Single-pixel detectors can be used to reconstruct three-dimensional images after patterned illumination of an object.

[Also see Report by

Sun
et al.

]
Robert G. Edwards (1925–2013)
Authors: Fisher Susan J. , Giudice Linda C.
Published: May 2013

The work of a pioneer of in vitro fertilization led to the first "test-tube baby" and changed the field of human reproductive biology.
Human Stem Cells From Cloning, Finally
Authors: Vogel Gretchen
Published: May 2013

This time it looks like it's for real: Researchers have made personalized human embryonic stem cells with a method similar to how Dolly the sheep was cloned—though with an added jolt of caffeine.
Systematic Review and Meta-Analysis of a Urine-Based Pneumococcal Antigen Test for Diagnosis of Community-Acquired Pneumonia Caused by Streptococcus pneumoniae
Authors: Sinclair Alison , Xie Xuanqian , Teltscher Marty , Dendukuri Nandini
Published: May 2013

Standard culture methods for diagnosis ofStreptococcus pneumoniaepneumonia take at least 24 h. The BinaxNOW urine-based test forS. pneumoniae(BinaxNOW-SP) takes only 15 min to conduct, potentially enabling earlier diagnosis and targeted treatment. This study was conducted to assess whether the use of BinaxNOW-SP at the time of hospital admission would provide adequate sensitivity and specificity for diagnosis of community-acquired pneumonia (CAP) in adult patients. We searched PubMed, EMBASE/OVID, Cochrane Collaboration, Centre for Reviews and Dissemination, INAHTA, and CADTH for diagnostic or etiologic studies of hospitalized predominately adult patients with clinically defined CAP that reported the diagnostic performance of BinaxNOW-SP versus cultures. Two authors independently extracted study details and diagnostic two-by-two tables. We found that 27 studies met our inclusion criteria, and three different reference standards were used between them. A bivariate meta-analysis of 12 studies using a composite of culture tests as the reference standard estimated the sensitivity of BinaxNOW-SP as 68.5% (95% credibility interval [CrI], 62.6% to 74.2%) and specificity as 84.2% (95% CrI, 77.5% to 89.3%). A meta-analysis of all 27 studies, adjusting for the imperfect and variable nature of the reference standard, gave a higher sensitivity of 74.0% (CrI, 66.6% to 82·3%) and specificity of 97.2% (CrI, 92.7% to 99.8%). The analysis showed substantial heterogeneity across studies, which did not decrease with adjustment for covariates. We concluded that the higher pooled sensitivity (compared to culture) and high specificity of BinaxNOW-SP suggest it would be a useful addition to the diagnostic workup for community-acquired pneumonia. More research is needed regarding the impact of BinaxNOW-SP on clinical practice.
Quantitation of Cytomegalovirus DNA Load in Dried Blood Spots Correlates Well with Plasma Viral Load
Authors: Limaye Ajit P. , Santo Hayes Tracy K. , Huang Meei-Li , Magaret Amalia , Boeckh Michael , Jerome Keith R.
Published: May 2013

An assay to accurately quantitate cytomegalovirus (CMV) load in finger-stick-collected dried blood spots (DBS) could potentially be useful for field studies or for analyzing patient self-collected specimens. We therefore assessed CMV DNA load in paired venipuncture-collected plasma samples and finger-stick DBS, using a previously validated quantitative PCR assay. Assay variability, sensitivity, and changes in viral load during antiviral therapy in finger-stick DBS were compared to the reference plasma quantitative PCR assay, using 106 prospectively collected pairs of finger-stick DBS and plasma samples from 35 solid-organ transplant (SOT) patients. The DBS assay showed good agreement with the reference plasma viral load assay on the log
10
scale (Pearson correlation coefficient, 0.92;
P
< 0.001). The 95% limit of detection of the DBS assay was estimated at 2,700 plasma copies/ml (675 plasma IU/ml). In 94% (76/81) of paired DBS and plasma samples above the limit of detection, the difference in CMV load was <1 log
10
. CMV viral load changes during antiviral treatment were comparable in plasma and DBS. We conclude that finger-stick DBS provides a convenient sample type for quantitation of CMV load that correlates well with plasma levels. Future studies to optimize and evaluate this methodology for patient self-collected samples are warranted.
Correlation of Leukorrhea and Trichomonas vaginalis Infection
Authors: Lazenby Gweneth B. , Soper David E. , Nolte Frederick S.
Published: May 2013

Trichomonas vaginalis
is a common sexually transmitted infection (STI) causing vaginitis. Microscopy has poor sensitivity but is used for diagnosis of trichomoniasis in resource-poor settings. We aimed to provide a more reliable diagnosis of trichomoniasis by investigating an association with leukorrhea. Women presenting for evaluation of vaginal discharge, STI exposure, or preventative gynecologic examination were evaluated for
Trichomonas
infection. Vaginal pH was determined and microscopy was performed by the provider, who recorded the number of polymorphonuclear leukocytes (PMNLs) per epithelial cell and the presence of clue cells, yeast, and/or motile trichomonads. Leukorrhea was defined as greater than one PMNL per epithelial cell. Culture and a nucleic acid amplification test (NAAT) were used to detect
T. vaginalis
. Patients were evaluated for
Chlamydia trachomatis
and
Neisseria gonorrhoeae
using NAATs and bacterial vaginosis using Gram stains. Two hundred ninety-four women were enrolled, and 16% were found to have
Trichomonas
(46/294).
Trichomonas
infection was more common in parous non-Hispanic, black women, who reported low rates of contraceptive use (33% versus 17%;
P
= 0.02) and a STI history (85% versus 55%;
P
= 0.002). These women were more likely to report vaginal discharge (76% versus 59%;
P
= 0.02) and have an elevated vaginal pH (87% versus 48%;
P
< 0.001) and gonorrhea infection (15% versus 4%;
P
= 0.002). Leukorrhea was associated with a 4-fold-increased risk of
Trichomonas
infection. Leukorrhea on microscopy was associated with
Trichomonas
vaginitis. Patients with leukorrhea should be evaluated with more-sensitive tests for
T. vaginalis
, preferably NAATs, if microscopy is negative.
Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients
Authors: Abate Davide , Saldan Alda , Mengoli Carlo , Fiscon Marta , Silvestre Cristina , Fallico Loredana , Peracchi Marta , Furian Lucrezia , Cusinato Riccardo , Bonfante Luciana , Rossi Barbara , Marchini Francesco , Sgarabotto Dino , Rigotti Paolo , Palù Giorgio
Published: May 2013

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R
+
) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D
+
/R
−
). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (
P
< 0.05). During the antiviral prophylaxis, all 20 D
+
/R
−
KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.
Subtyping of Salmonella enterica Serovar Newport Outbreak Isolates by CRISPR-MVLST and Determination of the Relationship between CRISPR-MVLST and PFGE Results
Authors: Shariat Nikki , Kirchner Margaret K. , Sandt Carol H. , Trees Eija , Barrangou Rodolphe , Dudley Edward G.
Published: May 2013

Salmonella entericasubsp.entericaserovar Newport (S. Newport) is the third most prevalent cause of food-borne salmonellosis. Rapid, efficient, and accurate methods for identification are required to track specific strains ofS. Newport during outbreaks. By exploiting the hypervariable nature of virulence genes and clustered regularly interspaced short palindromic repeats (CRISPRs), we previously developed a sequence-based subtyping approach, designated CRISPR–multi-virulence-locus sequence typing (CRISPR-MVLST). To demonstrate the applicability of this approach, we analyzed a broad set ofS. Newport isolates collected over a 5-year period by using CRISPR-MVLST and pulsed-field gel electrophoresis (PFGE). Among 84 isolates, we defined 38S. Newport sequence types (NSTs), all of which were novel compared to our previous analyses, and 62 different PFGE patterns. Our data suggest that both subtyping approaches have high discriminatory abilities (>0.95) with a potential for clustering cases with common exposures. Importantly, we found that isolates from closely related NSTs were often similar by PFGE profile as well, further corroborating the applicability of CRISPR-MVLST. In the first full application of CRISPR-MVLST, we analyzed isolates from a recentS. Newport outbreak. In this blinded study, we confirmed the utility of CRISPR-MVLST and were able to distinguish the 10 outbreak isolates, as defined by PFGE and epidemiological data, from a collection of 20S. Newport isolates. Together, our data show that CRISPR-MVLST could be a complementary approach to PFGE subtyping forS. Newport.
Rapid Detection of Human Cytomegalovirus UL97 and UL54 Mutations Directly from Patient Samples
Authors: Hall Sedlak Ruth , Castor Jared , Butler-Wu Susan M. , Chan Elaine , Cook Linda , Limaye Ajit P. , Jerome Keith R.
Published: May 2013

Human cytomegalovirus (CMV) is a significant contributor to morbidity and mortality in immunocompromised patients, particularly in the transplant setting. The availability of anti-CMV drugs has improved treatment, but drug resistance is an emerging problem. Here, we describe an improved, rapid, sequencing-based assay for the two genes in CMV where drug resistance occurs, the UL97 and UL54 genes. This assay is performed in 96-well format with a single master mix and provides clinical results within 2 days. It sequences codons 440 to 645 in the UL97 gene and codons 255 to 1028 in the UL54 gene with a limit of detection of 240 IU/ml. With this assay, we tested 43 specimens that had previously been tested for UL97 drug resistance and identified 3 with UL54 mutations. One of these patients had no concurrent UL97 mutation, pointing toward the need for an assay that facilitates dual UL97/UL54 gene testing for complete resistance profiling.
Comparative Evaluation of the Bruker Biotyper and Vitek MS Matrix-Assisted Laser Desorption Ionization–Time Of Flight (MALDI-TOF) Mass Spectrometry Systems for Identification of Yeasts of Medical Importance
Authors: Mancini Nicasio , De Carolis Elena , Infurnari Laura , Vella Antonietta , Clementi Nicola , Vaccaro Luisa , Ruggeri Alberto , Posteraro Brunella , Burioni Roberto , Clementi Massimo , Sanguinetti Maurizio
Published: May 2013

We report the first comparative evaluation between the Bruker Biotyper MS (BMS) and the Vitek MS (VMS) for the identification of yeasts. The rate of correct identifications at the species level was comparable using the commercial databases (89.8% versus 84.3%;
P
= 0.712), but higher for BMS using an in-house-extended database (100% versus 84.3%;
P
= 0.245). Importantly, the rate of misidentification was significantly higher for VMS (1% versus 12.1%;
P
< 0.0001), including the rate of major errors (0% versus 4.5%;
P
= 0.0036).
Intraventricular Hemorrhage and Multiple Intracranial Cysts Associated with Congenital Cytomegalovirus Infection
Authors: Suksumek Nithipun , Scott James N. , Chadha Rati , Yusuf Kamran
Published: May 2013

Intraventricular hemorrhage with congenital cytomegalovirus (CMV) infection is rare and has been reported only in extremely premature infants or in association with thrombocytopenia. We report the first case of a full-term male infant with congenital CMV infection and intraventricular hemorrhage with a normal platelet count and coagulation profile. The infant also had a left subependymal cyst and bilateral occipital cysts without any other manifestations of CMV infection.