bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of shock indicators for determining the need for blood transfusion after massive obstetric hemorrhage
Authors: Era Sumiko , Matsunaga Shigetaka , Matsumura Hideyoshi , Murayama Yoshihiko , Takai Yasushi , Seki Hiroyuki
Published: August 2014

Aim

Massive obstetric hemorrhage (MOH) requires prompt transfusion of red blood cells and coagulation factors. Because MOH has a diverse pathogenesis, the shock index (SI) alone may be insufficient for determining blood transfusion. Here, we retrospectively analyzed patients with MOH to determine usefulness of the indicators of shock including the SI in evaluating the need for blood transfusion.

Methods

We reviewed records of 80 emergency referral patients who had received blood transfusions at our department between 1 January 2009 and 31 July 2011. The shock indicators for blood transfusion are estimated blood loss, fibrinogen level, hemoglobin concentration, the Japan Society of Obstetrics and Gynecology disseminated intravascular coagulation (JSOG DIC) score and the SI. The strength of the correlation of each shock indicator with the transfusion volume was ranked using Spearman's rank correlation coefficient‐ρ and multivariate analysis.

Results

Although the SI showed significant positive correlation with blood transfusion volume for red blood cell concentrate (RCC) and fresh frozen plasma (FFP) in patients with dilutional coagulopathy, a stronger correlation was seen with the fibrinogen level and JSOG DIC score. In patients with consumptive coagulopathy, the strongest correlation was seen between RCC transfusion volume and fibrinogen level, and between FFP transfusion volume and JSOG DIC score followed by fibrinogen level. In multivariate analysis, only fibrinogen level was significantly associated with both RCC and FFP massive transfusion.

Conclusion

Because MOH has a diverse pathogenesis, various indicators should be evaluated. Among shock indicators, fibrinogen level was the best indicator of the need for blood transfusion following MOH.
Cardiovascular risk in patients with sleep apnoea with or without continuous positive airway pressure therapy: follow‐up of 4.5 million Danish adults
Authors: Lamberts M. , Nielsen O. W. , Lip G. Y. H. , Ruwald M. H. , Christiansen C. B. , Kristensen S. L. , Torp‐Pedersen C. , Hansen M. L. , Gislason G. H.
Published: August 2014

Background

The prognostic significance of age and continuous positive airway pressure (CPAP) therapy on cardiovascular disease in patients with sleep apnoea has not been assessed previously.

Methods

Using nationwide databases, the entire Danish population was followed from 2000 until 2011. First‐time sleep apnoea diagnoses and use of CPAP therapy were determined. Incidence rate ratios (IRRs) of ischaemic stroke and myocardial infarction (MI) were analysed using Poisson regression models.

Results

Amongst 4.5 million individuals included in the study, 33 274 developed sleep apnoea (mean age 53, 79% men) of whom 44% received persistent CPAP therapy. Median time to initiation of CPAP therapy was 88 days (interquartile range 34–346). Patients with sleep apnoea had more comorbidities compared to the general population. Crude rates of MI and ischaemic stroke were increased for sleep apnoea patients (5.4 and 3.6 events per 1000 person‐years compared to 4.0 and 3.0 in the general population, respectively). Relative to the general population, risk of MI [IRR 1.71, 95% confidence interval (CI) 1.57–1.86] and ischaemic stroke (IRR 1.50, 95% CI 1.35–1.66) was significantly increased in patients with sleep apnoea, in particular in patients younger than 50 years (IRR 2.12, 95% CI 1.64–2.74 and IRR 2.34, 95% CI 1.77–3.10, respectively). Subsequent CPAP therapy was not associated with altered prognosis.

Conclusions

Sleep apnoea is associated with increased risk of ischaemic stroke and MI, particularly in patients younger than 50 years of age. CPAP therapy was not associated with a reduced rate of stroke or MI.
The influence of sleep restriction on expression of apoptosis regulatory proteins p53, Bcl‐2 and Bax following rat tongue carcinogenesis induced by 4‐nitroquinoline 1‐oxide
Authors: Noguti Juliana , Alvarenga Tathiana A. , Marchi Patrícia , Oshima Celina T. F. , Andersen Monica L. , Ribeiro Daniel A.
Published: August 2014

Purpose

The aim of this study was to evaluate whether sleep restriction (SR) could affect the mechanisms and pathways’ essentials for cancer cells in tongue cancer induced by 4‐nitroquinoline 1‐oxide in Wistar rats.

Methods

The animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to sleep restriction for 21 days using the modified multiple platform method, which consisted of placing 5 rats in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl‐2 proteins related to apoptosis and its pathways.

Results

Although no histopathologic abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre‐neoplastic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53, and for bcl‐2. Following 12 weeks of 4NQO administration, we found significant differences between SR and control groups in p53, bax, and bcl‐2 immunoexpression.

Conclusion

Our results reveal that sleep restriction exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.
Association of Epstein‐Barr virus infection with oral squamous cell carcinoma in a case–control study
Authors: Acharya Sulav , Ekalaksananan Tipaya , Vatanasapt Patravoot , Loyha Kulchaya , Phusingha Pensiri , Promthet Supannee , Kongyingyoes Bunkerd , Pientong Chamsai
Published: August 2014

Background

Besides the well‐known risk factors, Epstein‐Barr virus (EBV) might play a significant role in oral squamous cell carcinoma (OSCC). To explore the role of EBV in OSCC, the prevalence of EBV infection in oral exfoliated cells of OSCC cases and controls in northeastern Thailand was investigated, and the association of EBV in tumor lesion cells was further confirmed.

Methods

Oral exfoliated cells were collected from OSCC cases and non‐cancer controls. Cells from tumor lesions were taken from OSCC patients for further strong confirmation of the association of EBV with OSCC. EBV DNA was detected by polymerase chain reaction (PCR) using primers specific for EBV DNA polymerase. The EBV DNA positive samples were confirmed further by nested PCR.

Results

Epstein‐Barr virus was detected in the oral exfoliated cells of 45.05% of OSCC patients and 18.08% of the non‐cancer control (P < 0.001). Similarly, EBV was detected in 32.5% of the tumor lesions. Betel quid chewing was statistically significantly associated with EBV prevalence (OR = 2.08), whereas no association with tobacco smoking and alcohol consumption. Alcohol consumption and betel quid chewing were significantly associated with OSCC (OR = 3.05 and OR = 5.05, respectively), but tobacco smoking was not associated. Interestingly, EBV was significantly associated with OSCC (OR = 3.76).

Conclusions

Epstein‐Barr virus prevalence is associated with OSCC and seems to be enhanced by betel quid chewing, suggesting that EBV may, together with betel quid chewing, act as an important etiological risk factor of OSCC.
Molecular characterization of immortalized normal and dysplastic oral cell lines
Authors: Dickman Christopher T. D. , Towle Rebecca , Saini Rajan , Garnis Cathie
Published: August 2014

Background

Cell lines have been developed for modeling cancer and cancer progression. The molecular background of these cell lines is often unknown to those using them to model disease behaviors. As molecular alterations are the ultimate drivers of cell phenotypes, having an understanding of the molecular make‐up of these systems is critical for understanding the disease biology modeled.

Methods

Six immortalized normal, one immortalized dysplasia, one self‐immortalized dysplasia, and two primary normal cell lines derived from oral tissues were analyzed for DNA copy number changes and changes in both mRNA and miRNA expression using SMRT‐v.2 genome‐wide tiling comparative genomic hybridization arrays, Agilent Whole Genome 4x44k expression arrays, and Exiqon V2.M‐RT‐PCR microRNA Human panels.

Results

DNA copy number alterations were detected in both normal and dysplastic immortalized cell lines—as well as in the single non‐immortalized dysplastic cell line. These lines were found to have changes in expression of genes related to cell cycle control as well as alterations in miRNAs that are deregulated in clinical oral squamous cell carcinoma tissues. Immortal lines—whether normal or dysplastic—had increased disruption in expression relative to primary lines. All data are available as a public resource.

Conclusions

Molecular profiling experiments have identified DNA, mRNA, and miRNA alterations for a panel of normal and dysplastic oral tissue cell lines. These data are a valuable resource to those modeling diseases of the oral mucosa, and give insight into the selection of model cell lines and the interpretation of data from those lines.
Elevated CO2 concentration impacts cell wall polysaccharide composition of green microalgae of the genus Chlorella
Authors: Cheng Y.-S. , Labavitch J.M. , VanderGheynst J.S.
Published: August 2014

The effect of CO2 concentration on the relative content of starch, lipid and cell wall carbohydrates in microalgal biomass was investigated for the four following Chlorella strains: C. vulgaris (UTEX 259), C. sorokiniana (UTEX 2805), C. minutissima (UTEX 2341) and C. variabilis (NC64A). Each strain had a different response to CO2 concentration. The starch content was higher in UTEX259 and NC64A cultured with 2% CO2 in the air supply than in cells cultured with ca. 0·04% CO2 (ambient air), while starch content was not affected for UTEX 2805 and UTEX 2341. The lipid content was higher in Chlorella minutissima UTEX 2341 cultured in 2% CO2 than in cells cultured in ambient air, but was unchanged for the other three strains. All four Chlorella strains tended to have a higher percentage of uronic acids and lower percentage of neutral sugars in their cell wall polysaccharide complement when grown with 2% CO2 supply. Although the percentage of neutral sugars in the cell walls varied with CO2 concentration, the relative proportions of different neutral sugar constituents remained constant for both CO2 conditions. The results demonstrate the importance of considering the effects of CO2 on the cell wall carbohydrate composition of microalgae.

Significance and Impact of the Study

Microalgae have the potential to produce products that will reduce society's reliance on fossil fuels and address challenges related to food and feed production. An overlooked yet industrially relevant component of microalgae are their cell walls. Cell wall composition affects cell flocculation and the recovery of intracellular products. In this study, we show that increasing CO2 level results in greater cell wall polysaccharide and uronic acid content in the cell walls of three strains of microalgae. The results have implications on the management of systems for the capture of CO2 and production of fuels, chemicals and food from microalgae.
The genetics of a putative social trait in natural populations of yeast
Authors: Bozdag G. O. , Greig D.
Published: August 2014

The sharing of secreted invertase by yeast cells is a well‐established laboratory model for cooperation, but the only evidence that such cooperation occurs in nature is that the SUC loci, which encode invertase, vary in number and functionality. Genotypes that do not produce invertase can act as ‘cheats’ in laboratory experiments, growing on the glucose that is released when invertase producers, or ‘cooperators’, digest sucrose. However, genetic variation for invertase production might instead be explained by adaptation of different populations to different local availabilities of sucrose, the substrate for invertase. Here we find that 110 wild yeast strains isolated from natural habitats, and all contained a single SUC locus and produced invertase; none were ‘cheats’. The only genetic variants we found were three strains isolated instead from sucrose‐rich nectar, which produced higher levels of invertase from three additional SUC loci at their subtelomeres. We argue that the pattern of SUC gene variation is better explained by local adaptation than by social conflict.
Immunocytochemical analysis of glucose transporter protein‐1 (GLUT‐1) in typical, brain invasive, atypical and anaplastic meningioma
Authors: van de Nes Johannes A. P. , Griewank Klaus G. , Schmid Kurt‐Werner , Grabellus Florian
Published: August 2014

Glucose transporter‐1 (GLUT‐1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT‐1 in intracranial non‐embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT‐1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet‐like growth, prominent nucleoli, small cell change and “spontaneous” necrosis. The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT‐1 expression was found to be mainly weak in WHO grade I meningiomas (IRS = 1–4) and to be consistently strong in WHO grade III meningiomas (IRS = 6–12), in WHO grade II meningiomas GLUT‐1 expression was variable (IRS = 1–9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT‐1 expression as observed in WHO grade I meningiomas (IRS = 0–4). (3) GLUT‐1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I‐III meningiomas, while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in angiomatous WHO grade I meningioma. (4) “Spontaneous” necrosis and small cell change typically occurred away from the intratumoral capillary network embedded within the pattern of GLUT‐1 staining. Taken together, GLUT‐1 staining cannot be applied as a substitute for histologic grading in order to predict tumor behavior. However, assessment of tumor hypoxia in association with “spontaneous” necrosis and foci of small cell change may substantially contribute to the neuropathologic diagnosis of WHO grades II and III meningioma.
The role of post‐floral persistent perianth in Helleborus viridis subsp. occidentalis (Ranunculaceae)
Authors: Guitián Javier , Larrinaga Asier R.
Published: August 2014

Species within the genus Helleborus differ in the relative location of their sepals. Previous studies have proved the existence of post‐floral functionality of sepals in H. foetidus, which leads us to consider the possibility of differences in the functionality of the sepals in H. viridis subsp. occidentalis. In this study, we analyzed their influence on the number and weight of seeds through experimental manipulations, which involve a progressive reduction of sepals following fertilization. Our results show that different levels of perianth reduction have no effect on the number and weight of seeds in Helleborus viridis subsp. occidentalis. We propose that differences in the timing of leaf development and changes in the position of floral organs among the different Helleborus species, underlie a distinctive response to the ever‐changing weather conditions of the European winters and springs.
ONLY GOOD FENCES KEEP GOOD NEIGHBOURS! THE INSTITUTIONALIZATION OF MINISTRY–AGENCY RELATIONSHIPS AT THE SCIENCE–POLICY NEXUS IN GERMAN FOOD SAFETY POLICY
Authors: KORINEK REBECCA‐LEA , VEIT SYLVIA
Published: August 2014

This article makes a further contribution to opening the ‘black box’ of micropractices in ministry–agency relationships. We argue that the mechanisms that come into play in the course of institutionalizing agencification reforms – such as renegotiating mutual roles and rules in ministry–agency interactions – are only poorly covered in the existing literature. To adequately address the negotiated and contingent nature of de facto agency autonomy and political control, we develop an interpretive approach based on the concept of ‘boundary work’. The empirical focus is on ministry–agency interactions at the science–policy nexus in the contested policy field of food safety. By studying actors' stories about the institutionalization processes following the fundamental reorganization of the German food safety administration in the wake of the BSE crisis from a longitudinal perspective, we show how actors manage boundary conflicts via increasingly differentiated backstage coordination.
Brain metastasis is predetermined in early stages of cutaneous melanoma by CD44v6 expression through epigenetic regulation of the spliceosome
Authors: Marzese Diego M. , Liu Michelle , Huynh Jamie L. , Hirose Hajime , Donovan Nicholas C. , Huynh Kelly T. , Kiyohara Eiji , Chong Kelly , Cheng David , Tanaka Ryo , Wang Jinhua , Morton Donald L. , Barkhoudarian Garni , Kelly Daniel F. , Hoon Dave S. B.
Published: August 2014

Melanoma brain metastasis (MBM) is frequent and has a very poor prognosis with no current predictive factors or therapeutic molecular targets. Our study unravels the molecular alterations of cell‐surface glycoprotein CD44 variants during melanoma progression to MBM. High expression of CD44 splicing variant 6 (CD44v6) in primary melanoma (PRM) and regional lymph node metastases from AJCC Stage IIIC patients significantly predicts MBM development. The expression of CD44v6 also enhances the migration of MBM cells by hyaluronic acid and hepatocyte growth factor exposure. Additionally, CD44v6‐positive MBM migration is reduced by blocking with a CD44v6‐specific monoclonal antibody or knocking down CD44v6 by siRNA. ESRP1 and ESRP2 splicing factors correlate with CD44v6 expression in PRM, and ESRP1 knockdown significantly decreases CD44v6 expression. However, an epigenetic silencing of ESRP1 is observed in metastatic melanoma, specifically in MBM. In advanced melanomas, CD44v6 expression correlates with PTBP1 and U2AF2 splicing factors, and PTBP1 knockdown significantly decreases CD44v6 expression. Overall, these findings open a new avenue for understanding the high affinity of melanoma to progress to MBM, suggesting CD44v6 as a potential MBM‐specific factor with theranostic utility for stratifying patients.
Differential effect of body mass index on pediatric heart transplant outcomes based on diagnosis
Authors: Godown Justin , Donohue Janet E. , Yu Sunkyung , Friedland‐Little Joshua M. , Gajarski Robert J. , Schumacher Kurt R.
Published: August 2014

The impact of nutritional status on HTx waitlist mortality in children is unknown, and there are conflicting data regarding the role of nutrition in post‐HTx survival. This study examined the influence of nutrition on waitlist and post‐HTx outcomes in children. Children 2–18 yr listed for HTx from 1997 to 2011 were identified from the OPTN database and stratified by BMI percentile. Multivariable logistic regression evaluated the influence of BMI on waitlist mortality. Cox proportional hazard regression assessed the impact of BMI on post‐HTx mortality. When all 2712 patients were analyzed, BMI did not impact waitlist, one‐, or five‐yr mortality. However, when stratified by diagnosis, BMI > 95% (AOR 1.96; 95% CI 1.24, 3.09) and BMI < 1% (AOR 2.17; 95% CI 1.28, 3.68) were independent risk factors for waitlist mortality in patients with CM. BMI did not impact waitlist mortality in CHD and did not impact post‐HTx outcomes, regardless of diagnosis. BMI > 95% and BMI < 1% are independent risk factors for waitlist mortality in patients with CM, but not CHD. This suggests differing risk factors based on disease etiology, and an individualized approach to risk assessment based on diagnosis may be warranted.
Increasing first‐time blood donation of newly registered donors using implementation intentions and explicit commitment techniques
Authors: Wevers A. , Wigboldus D. H. J. , van den Hurk K. , van Baaren R. , Veldhuizen I. J. T.
Published: August 2014

Background and Objectives

Most blood donors stop donating blood at the beginning of their donor career. This intervention study aims to increase first‐time return behaviour of newly registered donors using implementation intentions and explicit commitment techniques.

Materials and Methods

Newly registered donors (N = 937) received an extra information sheet during their medical check‐up wherein implementation intentions and explicit commitment techniques were tested. Donors were randomly assigned to either the control condition, information sheet only condition, information sheet with implementation intentions condition, information sheet with explicit commitment condition, or information sheet with both implementation intentions and explicit commitment condition. Logistic regression analyses examined actual first‐time return behaviour after an appeal to donate blood.

Results

Donors in the information sheet with both implementation intentions and explicit commitment condition had an 11·5% higher return rate than donors in the control condition. Logistic regression analyses revealed that the information sheet with both implementation intentions and explicit commitment condition significantly increased the odds on return behaviour compared with the control condition (OR = 1·65, 95%CI = 1·08–2·50).

Conclusion

This study successfully increased actual first‐time return behaviour of newly registered donors by using both implementation intentions and explicit commitment techniques.
Automated identification of retinal vessels using a multiscale directional contrast quantification (MDCQ) strategy
Authors: Zhen Yi , Gu Suicheng , Meng Xin , Zhang Xinyuan , Zheng Bin , Wang Ningli , Pu Jiantao
Published: August 2014

Purpose:

A novel algorithm is presented to automatically identify the retinal vessels depicted in color fundus photographs.

Methods:

The proposed algorithm quantifies the contrast of each pixel in retinal images at multiple scales and fuses the resulting consequent contrast images in a progressive manner by leveraging their spatial difference and continuity. The multiscale strategy is to deal with the variety of retinal vessels in width, intensity, resolution, and orientation; and the progressive fusion is to combine consequent images and meanwhile avoid a sudden fusion of image noise and/or artifacts in space. To quantitatively assess the performance of the algorithm, we tested it on three publicly available databases, namely, DRIVE, STARE, and HRF. The agreement between the computer results and the manual delineation in these databases were quantified by computing their overlapping in both area and length (centerline). The measures include sensitivity, specificity, and accuracy.

Results:

For the DRIVE database, the sensitivities in identifying vessels in area and length were around 90% and 70%, respectively, the accuracy in pixel classification was around 99%, and the precisions in terms of both area and length were around 94%. For the STARE database, the sensitivities in identifying vessels were around 90% in area and 70% in length, and the accuracy in pixel classification was around 97%. For the HRF database, the sensitivities in identifying vessels were around 92% in area and 83% in length for the healthy subgroup, around 92% in area and 75% in length for the glaucomatous subgroup, around 91% in area and 73% in length for the diabetic retinopathy subgroup. For all three subgroups, the accuracy was around 98%.

Conclusions:

The experimental results demonstrate that the developed algorithm is capable of identifying retinal vessels depicted in color fundus photographs in a relatively reliable manner.
Comment on “The hologenomic basis of speciation: Gut bacteria cause hybrid lethality in the genus
Nasonia
”
Authors: Chandler James Angus , Turelli Michael
Published: August 2014

Brucker and Bordenstein (Reports, 9 August 2013, p. 667) claim that adaptive codivergence of gut bacteria with hosts contributes to hybrid lethality. Yet, they provide no evidence for coadaptation of bacteria and
Nasonia
hosts. Their data on hybrid viability suggest that bacteria contribute to inviability only because intrinsic hybrid dysfunction increases susceptibility to free-living bacteria. Hologenomic speciation remains testable speculation without experimental support.
Targeted enhancement of cortical-hippocampal brain networks and associative memory
Authors: Wang Jane X. , Rogers Lynn M. , Gross Evan Z. , Ryals Anthony J. , Dokucu Mehmet E. , Brandstatt Kelly L. , Hermiller Molly S. , Voss Joel L.
Published: August 2014

Brain stimulation to improve human memory

The hippocampus is a crucial brain area for certain types of memory. Working with humans, Wang
et al.
found that a specific type of non-invasive brain stimulation improved memory tests and enhanced information flow between the hippocampus and a number of other brain regions. This increased connectivity was highly specific for the individual target areas selected for each participant.

Science
, this issue p.
1054
Demystifying central government R&D spending in China
Authors: Sun Yutao , Cao Cong
Published: August 2014

Should funding focus on scientific research?
Longitudinal analysis of microbial interaction between humans and the indoor environment
Authors: Lax Simon , Smith Daniel P. , Hampton-Marcell Jarrad , Owens Sarah M. , Handley Kim M. , Scott Nicole M. , Gibbons Sean M. , Larsen Peter , Shogan Benjamin D. , Weiss Sophie , Metcalf Jessica L. , Ursell Luke K. , Vázquez-Baeza Yoshiki , Van Treuren Will , Hasan Nur A. , Gibson Molly K. , Colwell Rita , Dantas Gautam , Knight Rob , Gilbert Jack A.
Published: August 2014

Signature microbes follow you from house to house

Householders share more than habitation; they also share inhabitants. In a diverse sample of U.S. homes, Lax
et al.
found that people and animals sharing homes shared their microbial communities (microbiota) too, probably because of skin shedding and hand and foot contamination. When families moved, their microbiological “aura” followed. If one person left the home even for a few days, their contribution to the microbiome diminished. These findings have implications not only for household identity and composition, but also for indicators of the members' health and well-being.

Science
, this issue p.
1048
A VLBI resolution of the Pleiades distance controversy
Authors: Melis Carl , Reid Mark J. , Mioduszewski Amy J. , Stauffer John R. , Bower Geoffrey C.
Published: August 2014

Distance score settled for Seven Sisters

Most of us have seen the Pleiades star cluster in the night sky, one of the few groups of physically related stars that are separately visible to the naked eye. In spite of its proximity to us, its distance has been disputed. Melis
et al.
settle the controversy with astrometric measurements from radio interferometry that reveal a distance of 136.2 parsecs (see the Perspective by Girardi). Other methods yielded similar values, but the trusted astrometry satellite Hipparcos measured only 120.2 parsecs. The new result alleviates the concern that astronomers would need to adjust their stellar evolution models to align with the Hipparcos distance.

Science
, this issue p.
1029
; see also p.
1001
Growth of nitrite-oxidizing bacteria by aerobic hydrogen oxidation
Authors: Koch Hanna , Galushko Alexander , Albertsen Mads , Schintlmeister Arno , Gruber-Dorninger Christiane , Lücker Sebastian , Pelletier Eric , Le Paslier Denis , Spieck Eva , Richter Andreas , Nielsen Per H. , Wagner Michael , Daims Holger
Published: August 2014

Oxidizing hydrogen in place of nitrite

Microorganisms are important drivers of Earth's nitrogen cycle. Many of the organisms responsible for mediating the reactions of one phase of nitrogen to another are thought to be ecologic specialists. Using a combination of genomic and experimental analyses, Koch
et al.
show that
Nitrospira moscoviensis
, a member of a widely distributed genus of nitrite-oxidizing bacteria, can oxidize hydrogen instead of nitrite to support growth when oxygen is present. Not only does this ecologic flexibility suggest a broader distribution of these organisms in natural settings, but they may be important in engineered environments as well.

Science
, this issue p.
1052
Dynamic signaling by T follicular helper cells during germinal center B cell selection
Authors: Shulman Ziv , Gitlin Alexander D. , Weinstein Jason S. , Lainez Begoña , Esplugues Enric , Flavell Richard A. , Craft Joseph E. , Nussenzweig Michel C.
Published: August 2014

T and B cells' intricate molecular dance

Generating high-affinity antibodies to fight infection is no easy task. To do so requires multiple steps, including T cells interacting with antibody-producing B cells in lymph nodes. These interactions select B cells expressing high-affinity antibodies for further proliferation, ensuring that the immune response generates high-affinity antibodies in large quantities. Shulman
et al.
use fluorescent live-cell imaging in mice to determine the molecular details of these interactions. They find that T cells engage B cells in short-lived mobile contacts during selection. These contacts cause T cells to flux calcium and produce proteins called cytokines, which probably drive B cells to proliferate and produce high-affinity antibodies.

Science
, this issue p.
1058
Australia needs a strategy
Authors: Chubb Ian
Published: August 2014

Australians are constantly told that our economy is ‘“in transition.”’ We need to move up the global value chain, build knowledge-based industries, prepare for the Asian Century, and be the “food bowl of the world.” These are grand ambitions that we share with many other nations, in our region and beyond. The question for all of us is: How?
Animal welfare accreditation called into question
Authors: Grimm David
Published: August 2014

PETA study finds violations more often in approved labs.
In search of Green Arabia
Authors: Lawler Andrew
Published: August 2014

Researchers are scouring the now-barren Arabian Peninsula to uncover its hidden role in ancient human migration.
Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy
Authors: Prince Harry E. , Lapé-Nixon Mary
Published: August 2014

The risk of intrauterine transmission of cytomegalovirus (CMV) during pregnancy is much greater for women who contract primary CMV infection after conception than for women with evidence of infection (circulating CMV antibodies) before conception. Thus, laboratory tests that aid in the identification of recent primary CMV infection are important tools for managing the care of pregnant women suspected of having been exposed to CMV. CMV IgM detection is a sensitive marker of primary CMV infection, but its specificity is poor because CMV IgM is also produced during viral reactivation and persists following primary infection in some individuals. Studies conducted over the last 20 years convincingly demonstrate that measurement of CMV IgG avidity is both a sensitive and a specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. IgG avidity is defined as the strength with which IgG binds to antigenic epitopes expressed by a given protein; it matures gradually during the 6 months following primary infection. Low CMV IgG avidity is an accurate indicator of primary infection within the preceding 3 to 4 months, whereas high avidity excludes primary infection within the preceding 3 months. In this minireview, we summarize published data demonstrating the clinical utility of CMV IgG avidity results for estimating time since primary infection in pregnant women, describe commercially available CMV IgG avidity assays, and discuss some of the issues and controversies surrounding CMV IgG avidity testing during pregnancy.
An International, Prospective, Multicenter Evaluation of the Combination of AdvanDx Staphylococcus
Quick
FISH BC with
mecA Xpress
FISH for Detection of Methicillin-Resistant Staphylococcus aureus Isolates from Positive Blood Cultures
Authors: Salimnia H. , Fairfax M. R. , Lephart P. , Morgan M. , Gilbreath J. J. , Butler-Wu S. M. , Templeton K. E. , Hamilton F. J. , Wu F. , Buckner R. , Fuller D. , Davis T. E. , Abdelhamed A. M. , Jacobs M. R. , Miller A. , Pfrommer B. , Carroll K. C.
Published: August 2014

Sepsis caused by
Staphylococcus aureus
is a major health problem worldwide. Better outcomes are achieved when rapid diagnosis and determination of methicillin susceptibility enable early optimization of antimicrobial therapy. Eight large clinical laboratories, seven from the United States and one from Scotland, evaluated the combination of the
Staphylococcus
Quick
FISH BC and the new
mecA Xpress
FISH assay (both AdvanDx, Woburn, MA, USA) for the detection of methicillin-resistant
S. aureus
in positive blood cultures. Blood cultures flagged as positive by automated blood culture instruments and demonstrating only Gram-positive cocci in clusters on Gram stain were tested by
Quick
FISH, a 20-min assay. If only
S. aureus
was detected,
mecA Xpress
FISH testing followed. The recovered
S. aureus
isolates were tested by cefoxitin disk diffusion as the reference method. The
Quick
FISH assay results were concordant with the routine phenotypic testing methods of the testing laboratories in 1,211/1,221 (99.1%) samples and detected 488/491
S. aureus
organisms (sensitivity, 99.4%; specificity, 99.6%). Approximately 60% of the samples (730) contained coagulase-negative staphylococci or nonstaphylococci as assessed by the
Quick
FISH assay and were not tested further. The 458 compliant samples positive exclusively for
S. aureus
by the
Quick
FISH assay were tested by the
mecA Xpress
FISH assay, which detected 209 of 211 methicillin-resistant
S. aureus
organisms (sensitivity, 99.1%; specificity, 99.6%). The
mecA Xpress
FISH assay also showed high reproducibility, with 534/540 tests performed by 6 operators over 5 days achieving reproducible results (98.9% agreement). The combination of the
Staphylococcus
Quick
FISH BC and
mecA Xpress
FISH assays is sensitive, specific, and reproducible for the detection of methicillin-resistant
S. aureus
and yields complete results in 2 h after the blood culture turns positive.
Evaluation of Anatomically Designed Flocked Rectal Swabs for Molecular Detection of Enteric Pathogens in Children Admitted to Hospital with Severe Gastroenteritis in Botswana
Authors: Goldfarb David M. , Steenhoff Andrew P. , Pernica Jeffrey M. , Chong Sylvia , Luinstra Kathy , Mokomane Margaret , Mazhani Loeto , Quaye Isaac , Goercke Irene , Mahony James , Smieja Marek
Published: August 2014

Two-hundred eighty matched bulk stool and anatomically designed flocked rectal swab samples were collected from children admitted to the hospital with acute diarrhea in Botswana. Their parents were asked about the acceptability of the swab collection method compared with bulk stool sampling. All samples underwent identical testing with a validated 15-target (9 bacterial, 3 viral, and 3 parasite) commercial multiplex PCR assay. The flocked swabs had a 12% higher yield for bacterial pathogen targets (241 versus 212;
P
= 0.003) compared with that of stool samples, as well as similar yields for viral targets (110 versus 113;
P
= 0.701) and parasite targets (59 versus 65;
P
= 0.345). One hundred sixty-four of the flocked swab-stool pairs were also tested with separate laboratory-developed bacterial and viral multiplex assays, and the flocked rectal swabs had a performance that was similar to that seen with commercial assay testing. Almost all parents/guardians found the swabs acceptable. Flocked rectal swabs significantly facilitate the molecular diagnosis of diarrheal disease in children.
Acceleration of Antimicrobial Susceptibility Testing of Positive Blood Cultures by Inoculation of Vitek 2 Cards with Briefly Incubated Solid Medium Cultures
Authors: Idelevich Evgeny A. , Schüle Isabel , Grünastel Barbara , Wüllenweber Jörg , Peters Georg , Becker Karsten
Published: August 2014

Briefly incubated agar cultures from positive blood cultures were used for antimicrobial susceptibility testing (AST) by Vitek 2. The cultivation time until inoculation was 3.8 h for Gram-positive cocci and 2.4 h for Gram-negative rods. The error rates were low, providing early and reliable AST without additional time or cost expenditure.
HIV Control Is Mediated in Part by CD8
+
T-Cell Targeting of Specific Epitopes
Authors: Pereyra Florencia , Heckerman David , Carlson Jonathan M. , Kadie Carl , Soghoian Damien Z. , Karel Daniel , Goldenthal Ariel , Davis Oliver B. , DeZiel Charles E. , Lin Tienho , Peng Jian , Piechocka Alicja , Carrington Mary , Walker Bruce D.
Published: August 2014

We investigated the hypothesis that the correlation between the class I HLA types of an individual and whether that individual spontaneously controls HIV-1 is mediated by the targeting of specific epitopes by CD8
+
T cells. By measuring gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay responses to a panel of 257 optimally defined epitopes in 341 untreated HIV-infected persons, including persons who spontaneously control viremia, we found that the correlation between HLA types and control is mediated by the targeting of specific epitopes. Moreover, we performed a graphical model-based analysis that suggested that the targeting of specific epitopes is a cause of such control—that is, some epitopes are protective rather than merely associated with control—and identified eight epitopes that are significantly protective. In addition, we use an
in silico
analysis to identify protein regions where mutations are likely to affect the stability of a protein, and we found that the protective epitopes identified by the ELISPOT analysis correspond almost perfectly to such regions. This
in silico
analysis thus suggests a possible mechanism for control and could be used to identify protective epitopes that are not often targeted in natural infection but that may be potentially useful in a vaccine. Our analyses thus argue for the inclusion (and exclusion) of specific epitopes in an HIV vaccine.

IMPORTANCE
Some individuals naturally control HIV replication in the absence of antiretroviral therapy, and this ability to control is strongly correlated with the HLA class I alleles that they express. Here, in a large-scale experimental study, we provide evidence that this correlation is mediated largely by the targeting of specific CD8
+
T-cell epitopes, and we identify eight epitopes that are likely to cause control. In addition, we provide an
in silico
analysis indicating that control occurs because mutations within these epitopes change the stability of the protein structures. This
in silico
analysis also identified additional epitopes that are not typically targeted in natural infection but may lead to control when included in a vaccine, provided that other epitopes that would otherwise distract the immune system from targeting them are excluded from the vaccine.
Stepwise Priming by Acidic pH and a High K
+
Concentration Is Required for Efficient Uncoating of Influenza A Virus Cores after Penetration
Authors: Stauffer Sarah , Feng Yuehan , Nebioglu Firat , Heilig Rosalie , Picotti Paola , Helenius Ari
Published: August 2014

Influenza A virus (IAV) uses the low pH in late endocytic vacuoles as a cue for penetration by membrane fusion. Here, we analyzed the prefusion reactions that prepare the core for uncoating after it has been delivered to the cytosol. We found that this priming process occurs in two steps that are mediated by the envelope-embedded M2 ion channel. The first weakens the interactions between the matrix protein, M1, and the viral ribonucleoprotein bundle. It involves a conformational change in a linker sequence and the C-terminal domain of M1 after exposure to a pH below 6.5. The second step is triggered by a pH of <6.0 and by the influx of K
+
ions. It causes additional changes in M1 as well as a loss of stability in the viral ribonucleoprotein bundle. Our results indicate that both the switch from Na
+
to K
+
in maturing endosomes and the decreasing pH are needed to prime IAV cores for efficient uncoating and infection of the host cell.

IMPORTANCE
The entry of IAV involves several steps, including endocytosis and fusion at late endosomes. Entry also includes disassembly of the viral core, which is composed of the viral ribonucleoproteins and the RNA genome. We have found that the uncoating process of IAV is initiated long before the core is delivered into the cytosol. M2, an ion channel in the viral membrane, is activated when the virus passes through early endosomes. Here, we show that protons entering the virus through M2 cause a conformational change in the matrix protein, M1. This weakens interactions between M1 and the viral ribonucleoproteins. A second change was found to occur when the virus enters late endosomes. The preacidified core is then exposed to a high concentration of K
+
, which affects the interactions between the ribonucleoproteins. Thus, when cores are finally delivered to the cytosol, they are already partially destabilized and, therefore, uncoating competent and infectious.
The Raccoon Polyomavirus Genome and Tumor Antigen Transcription Are Stable and Abundant in Neuroglial Tumors
Authors: Brostoff Terza , Dela Cruz Florante N. , Church Molly E. , Woolard Kevin D. , Pesavento Patricia A.
Published: August 2014

Raccoon polyomavirus (RacPyV) is associated with 100% of neuroglial tumors in free-ranging raccoons. Other tumor-associated polyomaviruses (PyVs), including simian virus 40 (SV40), murine PyV, and Merkel cell PyV, are found integrated in the host genome in neoplastic cells, where they constitutively express splice variants of the tumor antigen (TAg) gene. We have previously reported that RacPyV exists only as an episome (nonintegrated) in neuroglial tumors. Here, we have investigated TAg transcription in primary tumor tissue by transcriptome analysis, and we identified the alternatively spliced TAg transcripts for RacPyV. We also determined that TAg was highly transcribed relative to host cellular genes. We further colocalized TAg DNA and mRNA by
in situ
hybridization and found that the majority of tumor cells showed positive staining. Lastly, we examined the stability of the viral genome and TAg transcription by quantitative reverse transcriptase PCR in cultured tumor cells
in vitro
and in a mouse xenograft model. When tumor cells were cultured
in vitro
, TAg transcription increased nearly 2 log-fold over that of parental tumor tissue by passage 17. Both episomal viral genome and TAg transcription were faithfully maintained in culture and in tumors arising from xenotransplantation of cultured cells in mice. This study represents a minimal criterion for RacPyV's association with neuroglial tumors and a novel mechanism of stability for a polyomavirus in cancer.

IMPORTANCE
The natural cycle of polyomaviruses in mammals is to persist in the host without causing disease, but they can cause cancer in humans or in other animals. Because this is an unpredictable and rare event, the oncogenic potential of polyomavirus is primarily evaluated in laboratory animal models. Recently, raccoon polyomavirus (RacPyV) was identified in neuroglial tumors of free-ranging raccoons. Viral copy number was consistently high in these tumors but was low or undetectable in nontumor tissue or in unaffected raccoons. Unlike other oncogenic polyomaviruses, RacPyV was episomal, not integrated, in these tumors. To determine the stability of the viral genome and sustained transcription of the oncogenic tumor antigen genes, we cultured primary raccoon tumor cells and passaged them in mice, confirming the nonintegrated state of the virus and the maintenance of viral gene transcription throughout. RacPyV provides a naturally occurring and tractable model for a novel mechanism of polyomavirus-mediated oncogenesis.
Activation of Intrinsic Immune Responses and Microglial Phagocytosis in an
Ex Vivo
Spinal Cord Slice Culture Model of West Nile Virus Infection
Authors: Quick Eamon D. , Leser J. Smith , Clarke Penny , Tyler Kenneth L.
Published: August 2014

West Nile virus (WNV) is a neurotropic flavivirus that causes significant neuroinvasive disease involving the brain and/or spinal cord. Experimental mouse models of WNV infection have established the importance of innate and adaptive immune responses in controlling the extent and severity of central nervous system (CNS) disease. However, differentiating between immune responses that are intrinsic to the CNS and those that are dependent on infiltrating inflammatory cells has proven difficult. We used a murine
ex vivo
spinal cord slice culture (SCSC) model to determine the innate immune processes specific to the CNS during WNV infections. By 7 days after
ex vivo
infection of SCSCs, the majority of neurons and a substantial percentage of astrocytes were infected with WNV, resulting in apoptotic cell death and astrogliosis. Microglia, the resident immune cells of the CNS, were activated by WNV infection, as exemplified by their amoeboid morphology, the development of filopodia and lamellipodia, and phagocytosis of WNV-infected cells and debris. Microglial cell activation was concomitant with increased expression of proinflammatory cytokines and chemokines, including CXCL10, CXCL1, CCL5, CCL3, CCL2, tumor necrosis factor alpha (TNF-α), TNF-related apoptosis-inducing ligand (TRAIL), and interleukin-6 (IL-6). The application of minocycline, an inhibitor of neuroinflammation, altered the WNV-induced proinflammatory cytokine/chemokine expression profile, with inhibited production of CCL5, CCL2, and IL-6. Our findings establish that CNS-resident cells have the capacity to initiate a robust innate immune response against WNV infection in the absence of infiltrating inflammatory cells and systemic immune responses.

IMPORTANCE
There are no specific treatments of proven efficacy available for WNV neuroinvasive disease. A better understanding of the pathogenesis of WNV CNS infection is crucial for the rational development of novel therapies. Development of a spinal cord slice culture (SCSC) model facilitates the study of WNV pathogenesis and allows investigation of the intrinsic immune responses of the CNS. Our studies demonstrate that robust CNS innate immune responses, including microglial activation and proinflammatory cytokine/chemokine production, develop independently of contributions from the peripheral immune system and CNS-infiltrating inflammatory cells.