bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum proteomics of hepatitis C virus infection reveals retinol-binding protein 4 as a novel regulator
Authors: Gouthamchandra K. , Kumar Anuj , Shwetha Shivaprasad , Mukherjee Anirban , Chandra Madhavi , Ravishankar B. , Khaja M. N. , Sadhukhan Provash Chandra , Das Saumitra
Published: May 2014

Persistent infection of hepatitis C virus (HCV) can lead to liver cirrhosis and hepatocellular carcinoma, which are currently diagnosed by invasive liver biopsy. Approximately 15–20 % of cases of chronic liver diseases in India are caused by HCV infection. In North India, genotype 3 is predominant, whereas genotype 1 is predominant in southern parts of India. The aim of this study was to identify differentially regulated serum proteins in HCV-infected Indian patients (genotypes 1 and 3) using a two-dimensional electrophoresis approach. We identified eight differentially expressed proteins by MS. Expression levels of one of the highly upregulated proteins, retinol-binding protein 4 (RBP4), was validated by ELISA and Western blotting in two independent cohorts. We also confirmed our observation in the JFH1 infectious cell culture system. Interestingly, the HCV core protein enhanced RBP4 levels and partial knockdown of RBP4 had a positive impact on HCV replication, suggesting a possible role for this cellular protein in regulating HCV infection. Analysis of RBP4-interacting partners using a bioinformatic approach revealed novel insights into the possible involvement of RBP4 in HCV-induced pathogenesis. Taken together, this study provided information on the proteome profile of the HCV-infected Indian population, and revealed a link between HCV infection, RBP4 and insulin resistance.
The PI3K pathway acting on alternative HIV-1 pre-mRNA splicing
Authors: Hillebrand Frank , Erkelenz Steffen , Diehl Nora , Widera Marek , Noffke Juliane , Avota Elita , Schneider-Schaulies Sibylle , Dabauvalle Marie-Christine , Schaal Heiner
Published: May 2014

HIV-1 mediates pro-survival signals and prevents apoptosis via the phosphatidylinositol-3-kinase (PI3K) pathway. This pathway, however, also affects phosphorylation of serine-arginine (SR) proteins, a family of splicing regulatory factors balancing splice site selection. We now show that pharmacologic inhibition of PI3K signalling alters the HIV-1 splicing pattern of both minigene- and provirus-derived mRNAs. This indicates that HIV-1 might also promote PI3K signalling to balance processing of its transcripts by regulating phosphorylation of splicing regulatory proteins.
Functional knockout of forebrain protein 14-3-3 disrupts conditioned taste aversion learning
Authors: Kimbrough Adam , Wu Yuying , Zhou Yi , Houpt Thomas A.
Published: May 2014

Protein 14-3-3 isoforms are key to many cellular processes and are ubiquitous throughout the brain. 14-3-3 is a regulator of ser/thr phospho-signaling by binding and sequestering phosphorylated substrates including kinases, histone deactylases, and transcription factors. The role of protein 14-3-3 in conditioned taste aversion learning (CTA) has not previously been examined. We parameterized CTA learning in difopein- YFP transgenic mice, which have widespread by expression of the artificial peptide difopein in the forebrain, including the basolateral amygdala and insular cortex, resulting in functional knock-out (FKO) of all 14-3-3 isoforms . We found that a single pairing of saccharin or NaCl (CS) and LiCl injection (US) was not sufficient to induce CTA in FKO mice. Multiples pairings of CS and US did lead to CTA acquisition in the FKO mice; however, the CTA rapidly extinguished within 30 minutes to 24 hours after acquisition. Additionally, we found that 14-3-3 FKO mice have an attenuated visceral neuraxis response to LiCl as measured by c-Fos induction. The deficit in FKO was not due to an inability to discriminate or avoid tastants, because they showed normal unconditioned taste preferences for both palatable (saccharin, maltodextrin , low concentration NaCl) and unpalatable tastants (quinine, HCl, and high concentration NaCl) and they were able to reduce intake of a maltodextrin solution adulterated with quinine. The FKO did not have a global deficit in ingestive learning, because they were able to form a conditioned flavor-nutrient preference. Thus, FKO of forebrain 14-3-3 appears to disrupt CTA learning leading to forgetting, rapid extinction, or failure to reconsolidate. This further implicates ser/thr phospho-signaling pathways in the regulation of long-term CTA learning.
The impact of widespread regulatory neofunctionalization on homeolog gene evolution following whole-genome duplication in maize
Authors: Hughes Thomas E. , Langdale Jane A. , Kelly Steven
Published: May 2014

Whole-genome duplications are a widespread feature of plant genome evolution, having been detected in all flowering plant lineages. Despite the prevalence of these events, the extent to which duplicated genes (homeolog gene pairs) functionally diverge (neofunctionalization) is unclear. We present a genome-wide analysis of molecular evolution and regulatory neofunctionalization in maize (Zea maysL.). We demonstrate that 13% of all homeolog gene pairs in maize are regulatory neofunctionalized in leaves, and that regulatory neofunctionalized genes experience enhanced purifying selection. We show that significantly more genes have been regulatory neofunctionalized in foliar leaves than in husk leaves and that both leaf types have experienced selection for distinct functional roles. Furthermore, we demonstrate that biased subgenome expression dominance occurs only in the presence of regulatory neofunctionalization and that in nonregulatory neofunctionalized genes subgenome dominance is progressively acquired during development. Taken together, our study reveals several novel insights into the evolution of maize, genes, and gene expression, and provides a general model for gene evolution following whole-genome duplication in plants.
Limited Mouse Necropsy
Authors: Cardiff Robert D. , Miller Claramae H. , Munn Robert J.
Published: May 2014

Procurement of mouse tissues or organs is essential for complete verification of almost any phenotype. A proper necropsy can yield information that is difficult to obtain by limited biopsy or surgical intervention. The protocol described here is for a limited autopsy involving the thorax and abdomen only, and does not include all organs.
Immunostaining for Markers of Apoptosis in the Caenorhabditis elegans Germline
Authors: Lant Benjamin , Derry W. Brent
Published: May 2014

The transparency of Caenorhabditis elegans makes it an ideal organism for visualizing proteins by immunofluorescence microscopy; however, the tough cuticle of worms and the egg shell surrounding embryos pose challenges in achieving effective fixation so that antibodies can diffuse into cells. In this protocol, we describe immunostaining of apoptosis-related proteins in the C. elegans adult germline using fluorescent reagents. Protein localization and abundance can be determined in various mutant backgrounds and under a variety of conditions, such as exposure to genotoxic stress. The number of antibodies specific to C. elegans proteins is quite limited compared with other organisms, but there is a growing list of immunological reagents directed against proteins in other organisms that cross-react with the homologous C. elegans proteins.
Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progressions with Fucci Technology
Authors: Sakaue-Sawano Asako , Miyawaki Atsushi
Published: May 2014

The visualization of cell-cycle behavior of individual cells within complex tissues presents an irresistible challenge to biologists studying multicellular structures. However, the transition from G1 to S in the cell cycle is difficult to monitor despite the fact that the process involves the critical decision to initiate a new round of DNA replication. Here, we use ubiquitination oscillators that control cell-cycle transitions to develop genetically encoded fluorescent probes for cell-cycle progression. Fucci (fluorescent ubiquitination-based cell-cycle indicator) probes exploit the regulation of cell-cycle-dependent ubiquitination to effectively label individual nuclei in G1 phase red, and those in S/G2/M phases green. Cultured cells and transgenic mice constitutively expressing the probes have been generated, such that every cell nucleus shows either red or green fluorescence. This protocol details two experiments that use biological samples expressing Fucci probes. One experiment involves time-lapse imaging of cells stably expressing a Fucci derivative (Fucci2), which allows for the exploration of the spatiotemporal patterns of cell-cycle dynamics during structural and behavioral changes of cultured cells. The other experiment involves large-field, high-resolution imaging of fixed sections of Fucci transgenic mouse embryos, which provides maps that illustrate cell proliferation versus differentiation in various developing organs.
Generation of Transgenic Drosophila Expressing shRNAs in the miR-1 Backbone
Authors: Chang Kenneth , Marran Krista , Valentine Amy , Hannon Gregory J.
Published: May 2014

In Drosophila, long-term effects of RNA interference (RNAi) must be achieved by integrating into the genome a template from which an RNAi trigger is transcribed by cellular RNA polymerases, generally RNA polymerase II or III. With encoded triggers, not only can essentially permanent silencing be achieved, but control can also be exerted over the level of trigger expression, with a resulting variation in the degree to which the target is silenced. Knockdown can also be controlled in a temporal and cell-type-dependent fashion through the use of well-established transgenic methodologies and well-tested promoters. The forms of encoded triggers vary. Long double-stranded RNAs can be expressed as extended inverted repeats. The nearest equivalent of a small interfering RNA is an artificial microRNA (miRNA) or short hairpin RNA (shRNA), where a natural miRNA backbone (also called a scaffold) is remodeled to produce a different small RNA or a small inverted repeat (<30 nucleotides) is simply expressed. This protocol describes creation of transgenic Drosophila carrying shRNA inserts in a remodeled endogenous miRNA backbone. The protocol applies to the use of miRNA-based shRNAs, but most of the vectors, principles of experimental design, and methods are also applicable to long inverted repeat transgenes.
Assuming Free Speech
Authors: Kenyon Andrew T
Published: May 2014

Free speech is commonly seen in negative terms as a limitation on government action that restricts speech. Although there have long been arguments that government also has an obligation to act in support of free speech – in part because common free speech rationales appear to involve more than a negative right – much free speech law adopts a negative understanding. This article examines assumptions within negative approaches to free speech and finds little reason to support the idea that free speech exists primarily when the state is not directly limiting speech. On this analysis, arguments about free speech should be reframed. New questions would emerge about what legal limitations and obligations should be applied in the name of free speech and through what methods. The limited recognition given to positive free speech by, for example, the European Court of Human Rights would warrant further development. Free speech would have important positive and negative aspects.
Strict Liability for Police Nonfeasance? TheKinghanReport on theRiot (Damages)Act 1886
Authors: Morgan Jonathan
Published: May 2014

TheRiot (Damages)Act 1886 imposes a no‐fault obligation on police forces to compensate owners of property damaged in rioting. Following the riots acrossEngland in 2011 an independentHomeOffice review, theKinghanReport, concluded that the fundamental principle of theAct should be retained, while the machinery should be modernised. TheReport conceives of theAct as a useful, if highly unusual, compensation scheme that may ease socio‐economic problems in riot‐prone areas. This article questions that position. Strict liability offers potential advantages in contentious claims against public authorities, providing an incentive for the police to perform their duty to keep the peace while averting the questioning of police decision‐making that claims in negligence would inevitably require. The best alternative to negligence liability might not be ‘no liability’ (the general position now at common law), or liability based on ‘serious fault’ (as theLawCommission proposed in 2008), but liability without fault.
Determination of Tert‐Butylhydroquinone in Vegetable Oils Using Surface‐Enhanced Raman Spectroscopy
Authors: Pan Yun , Lai Keqiang , Fan Yuxia , Li Chunying , Pei Lu , Rasco Barbara A. , Huang Yiqun
Published: May 2014

Monitoring the level of tert‐butylhydroquinone (TBHQ), a permissible antioxidant additive in edible vegetable oils in many countries, is important to ensure that oils and products that contain them comply with the relevant import regulations. Surface‐enhanced Raman spectroscopy (SERS) technology coupled with chemometric methods including partial least squares (PLS) and support vector machine (SVM) regression was applied to determine levels of TBHQ in spiked corn oils (0 to 500 mg/kg, n = 40) and commercial vegetable oils (0 to 99.7 mg/kg, n = 25). The lowest detectable concentration was 5 mg/L for TBHQ in standard solutions and 10 mg/kg of TBHQ in vegetable oils from various plant sources. The TBHQ levels predicted by the PLS or SVM model had a high correlation with actual TBHQ levels in commercial oil samples (SVM: R2 = 0.972, ratio of performance to deviation [RPD] = 5.55, root mean square error [RMSE] = 5.73 mg/kg; PLS: R2 = 0.976, RPD = 6.43, RMSE = 4.94 mg/kg), indicating great potential of SERS methods for detection and quantification of TBHQ in oils from a variety of sources.
A Survey on Position‐Based Simulation Methods in Computer Graphics
Authors: Bender Jan , Müller Matthias , Otaduy Miguel A. , Teschner Matthias , Macklin Miles
Published: May 2014

The dynamic simulation of mechanical effects has a long history in computer graphics. The classical methods in this field discretize Newton's second law in a variety of Lagrangian or Eulerian ways, and formulate forces appropriate for each mechanical effect: joints for rigid bodies; stretching, shearing or bending for deformable bodies and pressure, or viscosity for fluids, to mention just a few. In the last years, the class of position‐based methods has become popular in the graphics community. These kinds of methods are fast, stable and controllable which make them well‐suited for use in interactive environments. Position‐based methods are not as accurate as force‐based methods in general but they provide visual plausibility. Therefore, the main application areas of these approaches are virtual reality, computer games and special effects in movies. This state‐of‐the‐art report covers the large variety of position‐based methods that were developed in the field of physically based simulation. We will introduce the concept of position‐based dynamics, present dynamic simulation based on shape matching and discuss data‐driven upsampling approaches. Furthermore, we will present several applications for these methods.
Financial Contracts in PIPE Offerings: The Role of Expert Placement Agents
Authors: Bengtsson Ola , Dai Na
Published: May 2014

We examine how Private Investment in Public Equity (PIPE) contracts allocate contingent cash flow rights between investors and issuers and the role of placement agents in PIPE contract design. Issuers advised by expert agents agree to more investor‐friendly terms than issuers advised by nonexpert agents. Expert agents appear to help issuers understand the payoff consequences of negotiable terms. Moreover, expert agents allow issuers to negotiate more attractive pricing when they agree to investor‐friendly terms. Issuers earn higher postoffering stock returns when they use expert agents or agree to more investor‐friendly terms. These results suggest that the involvement of expert agents is beneficial to PIPE issuers.
Capsule endoscopy in diagnosis of small bowel diseases: a health technology assessment
Authors: Li Xiang Lian , Shen Jian Tong , Li You Ping , Tang Cheng Wei , Huang Li Bin , Li Cui Cui , Yu Jia Jie , Wang Ying Jiang , Yang Zong Xia
Published: May 2014

Objectives

Capsule endoscopy (CE) has been widely used in the diagnosis of small bowel disease (SBD) in the world. To bring CE into the national health insurance directory, and intensify its popularization in primary hospital, the government needs high‐quality HTA evidence for decision makers. We were appointed by the National Health and Family Planning Commission of China to evaluate the effectiveness, safety, economy, and applicability of CE in the diagnosis of SBD, to provide the best currently available evidence for decision making.

Methods

We searched the Cochrane Library (Issue 8, 2013), PubMed, EMbase, INAHTA, VIP, CBM, CNKI and WanFang Data. All confirmed or suspected SBD patients with diagnosis by CE versus other alternative therapies were considered. Health technology assessments (HTAs), systematic reviews (SRs), meta‐analyses, randomized controlled trials (RCTs), guidelines and economic studies were included. Two investigators selected studies, assessed the quality and extracted data independently, and a descriptive analysis was used.

Results

We included 4 HTAs, 11 SRs/meta‐analyses, 2 RCTs, 5 guidelines, and 10 economic studies for assessment. The results showed that the disease detection rate of CE was higher than that of many other traditional technologies and that the main adverse event for CE was retention (0.7% to 3.0%). These results were consistent with those of the guidelines. Comprehensive results of economic studies showed the superiority of CE compared with other technologies. As the first choice, CE can decrease potential costs, especially when used in outpatients.

Conclusions

(i) CE has advantages in diagnostic yield, safety, and cost in the diagnosis of SBD, but some limitations exist. It still needs more high‐quality evidence on CE diagnosis accuracy. (ii) When the government approves the introduction of CE in a hospital, many factors must be considered, such as the local disease burden, clinical demand, ability to pay, and staff. At the same time, it is necessary to standardize training for operating physicians, to reduce economic losses caused by poor technical ability of the medical staff.
A systematic assessment of the quality of systematic reviews/meta‐analyses in radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma
Authors: Wang Yingqiang , Luo Qianqian , Li Youping , Deng Shaolin , Li Xianglian , Wei Shiyou
Published: May 2014

Objectives

The systematic reviews (SRs) of radiofrequency ablation (RFA) versus hepatic resection (HR) for early hepatocellular carcinoma (HCC) are increasing with varies qualities. The aim of this study is to evaluate quality and their impacts on outcomes of these studies.

Methods

We searched six databases and five official websites to find the SRs of RFA versus HR for early HCC. The Overview Quality Assessment Questionnaire (OQAQ), the Cochrane Collaboration's tool, and modified MINORS score were applied to assess their quality for SRs, randomized (RCTs) and nonrandomized controlled trials (NRCTs), respectively.

Results

Nineteen SRs were included. The results showed that the overall quality was poor, with a mean OQAQ score of 3.3 and 95%CI 2.6 to 4.1, only five (26.3%) SRs were good quality, six (31.6%) misused the statistical models, and three of them changed outcome direction after modification. Five SRs taken retrospective studies as RCT. In addition, a total of 39 primary studies referenced by these 19 SRs were included. The results showed that 3 RCTs were leveled grade B, and 35 NRCTs were of moderate quality, with an estimated mean MINORS score of 15.0 and 95%CI 14.6 to 15.4.

Conclusions

The overall quality of SRs comparing the effects between RFA and HR for early HCC was poor. There was high heterogeneity and low evidence level. Physicians should take caution when applying the results from these studies to their clinical practice.
Sleep Duration in Midlife and Later Life in Relation to Cognition
Authors: Devore Elizabeth E. , Grodstein Francine , Duffy Jeanne F. , Stampfer Meir J. , Czeisler Charles A. , Schernhammer Eva S.
Published: May 2014

Objectives

To evaluate associations between sleep duration at midlife and later life and change in sleep duration over time and cognition in older women.

Design

Participants reported sleep duration in 1986 and 2000, and a subgroup of older participants began cognitive testing in 1995 to 2001; follow‐up testing was conducted three times, at 2‐year intervals.

Setting

Prospective Nurses' Health Study cohort.

Participants

Female nurses aged 70 and older free of stroke and depression at the initial cognitive assessment (N = 15,385).

Measurements

Validated, telephone‐based cognitive battery to measure cognitive function; four repeated assessments over 6 years were averaged to estimate overall cognition at older ages, and trajectories of cognitive change were evaluated over follow up.

Results

Extreme sleep durations in later life were associated with worse average cognition (P < .001 for the quadratic term for a global score averaging all six cognitive tests). For example, women sleeping 5 h/d or less had worse global cognition than those sleeping 7 h/d, as did women sleeping 9 h/d or more; differences were equivalent to nearly 2 additional years of age. Associations were similar, although slightly attenuated, for sleep duration in midlife. Women whose sleep duration changed by 2 h/d or more over time had worse cognition than women with no change in sleep duration (e.g., for the global score, P < .001 for the quadratic term). Sleep duration was not associated with trajectories of cognitive function over 6 years, which might be attributable to short follow‐up for detecting cognitive decline.

Conclusion

Extreme sleep durations at midlife and later life and extreme changes in sleep duration over time appear to be associated with poor cognition in older women.
New Oral Anticoagulants in Elderly Adults: Evidence from a Meta‐Analysis of Randomized Trials
Authors: Sardar Partha , Chatterjee Saurav , Chaudhari Shobhana , Lip Gregory Y. H.
Published: May 2014

Objectives

To evaluate the efficacy and safety of new oral anticoagulants (NOACs) in elderly adults.

Design

Meta‐analyses of randomized clinical trials (RCTs).

Setting

PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched from January 1, 2001, through March 30, 2013.

Participants

Elderly population (≥75) in RCTs comparing NOACs (rivaroxaban, apixaban, and dabigatran) with conventional therapy.

Measurements

Two authors reviewed the trials, and odds ratios (ORs) were calculated using a random effects model.

Results

Ten RCTs included 25,031 elderly participants. Risk of major or clinically relevant bleeding was not significantly different between NOACs and conventional therapy in elderly adults (OR = 1.02, 95% confidence interval = 0.73–1.43). Similar results were observed when comparing NOACs and pharmacologically active agents. In atrial fibrillation (AF) trials, NOACs were more effective than conventional therapy in prevention of stroke or systemic embolism in an elderly population with AF. In non‐AF trials, NOACs also had a significantly lower risk of venous thromboembolism (VTE) or VTE‐related death than conventional therapy in elderly adults. Analysis for individual NOACs showed that the NOAC was noninferior or more effective than conventional therapy for efficacy and safety outcomes.

Conclusion

In participants of clinical trials aged 75 and older, NOACs did not cause excess bleeding and were associated with equal or greater efficacy than conventional therapy.
Towards light-mediated sensing of bacterial comfort
Authors: Zafrilla G. , Iglesias A. , Marín M. , Torralba L. , Dorado-Morales P. , Racero J.L. , Alcaina J.J. , Morales L.J. , Martínez L. , Collantes M. , Gómez L. , Vilanova C. , Porcar M.
Published: May 2014

Bacterial comfort is central to biotechnological applications. Here, we report the characterization of different sensoring systems, the first step within a broader synthetic biology-inspired light-mediated strategy to determine Escherichia coli perception of environmental factors critical to bacterial performance. We did so by directly ‘asking’ bacterial cultures with light-encoded questions corresponding to the excitation wavelength of fluorescent proteins placed under the control of environment-sensitive promoters. We built four genetic constructions with fluorescent proteins responding to glucose, temperature, oxygen and nitrogen; and a fifth construction allowing UV-induced expression of heterologous genes. Our engineered strains proved able to give feedback in response to key environmental factors and to express heterologous proteins upon light induction. This light-based dialoguing strategy reported here is the first effort towards developing a human–bacteria interphase with both fundamental and applied implications.

Significance and Impact of the Study

The results we present here are at the core of a larger synthetic biology research effort aiming at establishing a dialogue with bacteria. The framework is to convert the human voice into electric pulses, these into light pulses exciting bacterial fluorescent proteins, and convert light-emission back into electric pulses, which will be finally transformed into synthetic voice messages. We report here the first results of the project, in the form of light-based determination of key parameters for bacterial comfort. The ultimate goal of this strategy is to combine different engineered populations to have a combined feedback from the pool.
Diagnostics for Respondent-Driven Sampling
Authors: Gile Krista J. , Johnston Lisa G. , Salganik Matthew J.
Published: May 2014

Respondent-driven sampling (RDS) is a widely used method for sampling from hard-to-reach human populations, especially populations at higher risk for human immunodeficiency virus or acquired immune deficiency syndrome. Data are collected through a peer referral process over social networks. RDS has proven practical for data collection in many difficult settings and has been adopted by leading public health organizations around the world. Unfortunately, inference from RDS data requires many strong assumptions because the sampling design is partially beyond the control of the researcher and not fully observable. We introduce diagnostic tools for most of these assumptions and apply them in 12 high risk populations. These diagnostics empower researchers to understand their RDS data better and encourage future statistical research on RDS sampling and inference.
Multiple Dimensions of Climate Change and Their Implications for Biodiversity
Authors: Garcia Raquel A. , Cabeza Mar , Rahbek Carsten , Araújo Miguel B.
Published: May 2014

Background

Changes in Earth’s climate over time can be measured in many ways. The different metrics available represent alternative dimensions of climate change, each with distinct implications for biodiversity conservation and other sectors. However, this diversity is rarely recognized. At any given locality, average temperature or precipitation can increase or decrease, extreme values can become more intense or frequent, and the timing of specific climatic events can shift. At the same time, climatic conditions are redistributed at broader spatial extents. Across sets of localities, particular climatic conditions can become more or less available and can shift closer or farther in position at different velocities. Metrics quantifying these and other dimensions of change are commonly used in basic and applied sciences. In ecological contexts, individual metrics have helped to explain the role of past climate changes in driving species diversity or extinctions and to forecast the exposure of biodiversity to future climate changes. Yet, a comparison of the many alternative metrics in use is lacking to gain understanding of their properties and guide their use in biodiversity assessments.

Advances

Our review demonstrates that six commonly used metrics of climate change show contrasting patterns under 21st-century climate forecasts across the world. For example, whereas polar climates are projected to warm and shrink in area, the tropics see the emergence of novel climatic conditions and undergo local changes in average climates beyond past variability. To help interpret metrics of climate change, our review critically assesses the ecological implications of different metrics. Supported by examples of empirical links between observed changes in biological systems and different dimensions of climate change, we outline a conceptual framework for classification of climate change metrics according to the types of threat and opportunity they are likely to impose on biodiversity. Climate changes at the locality level are often associated with demographic threats and opportunities at the population level, whereas changes across localities can have positive or negative implications for the size and the position of species’ ranges.

Outlook

Forecasting the long-term impacts of future climate changes on biodiversity is challenging, not least because the responses of organisms are contingent on demographic, physiological, and evolutionary mechanisms, as well as on the interaction with other human-induced stressors such as habitat fragmentation. Lack of data for the majority of species on Earth further hampers the use of available bioclimatic modeling methods. By contrast, the use of simple metrics of climate change is more easily scalable to wholesale biodiversity. When appropriately implemented, such examination can provide a first-order assessment of the challenges that species are potentially exposed to, and in many circumstances, it might be the only option available.
Evaluating Flood Resilience Strategies for Coastal Megacities
Authors: Aerts Jeroen C. J. H. , Botzen W. J. Wouter , Emanuel Kerry , Lin Ning , de Moel Hans , Michel-Kerjan Erwann O.
Published: May 2014

Integration of models for storms and floods, damages and protections, should aid resilience planning and investments.
Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes
Authors: Raj Towfique , Rothamel Katie , Mostafavi Sara , Ye Chun , Lee Mark N. , Replogle Joseph M. , Feng Ting , Lee Michelle , Asinovski Natasha , Frohlich Irene , Imboywa Selina , Von Korff Alina , Okada Yukinori , Patsopoulos Nikolaos A. , Davis Scott , McCabe Cristin , Paik Hyun-il , Srivastava Gyan P. , Raychaudhuri Soumya , Hafler David A. , Koller Daphne , Regev Aviv , Hacohen Nir , Mathis Diane , Benoist Christophe , Stranger Barbara E. , De Jager Philip L.
Published: May 2014

Immunogenetic Variation

Many genetic variants have been implicated in disease but their effects in function across tissues and cell-types remain to be resolved.

Raj
et al.

(p.
519
) present an analysis of expression quantative trait loci (eQTL) measuring messenger RNA levels and examined correlations between genotypes and gene expression in purified monocytes and T cells in healthy individuals of European, African, and Asian descent. Most, but not all, of the eQTLs and their effects on expression were shared between the populations, as well as a substantial proportion between the cell types. Links were found with disease-associated variants and loci that previous genome-wide analyses have implicated in neurodegenerative and autoimmune diseases.
Edge Nonlinear Optics on a MoS
2
Atomic Monolayer
Authors: Yin Xiaobo , Ye Ziliang , Chenet Daniel A. , Ye Yu , O’Brien Kevin , Hone James C. , Zhang Xiang
Published: May 2014

Optics On the Edge

The ability to isolate stable materials just one atom thick has provided the impetus for a new generation of thin films technologies. Often, the materials are conceptually imaged in the form of an artist's impression as single continuous layers—a single crystal sheet of atoms. Scanning probe and transmission electron microscopies reveal the reality, however, where the material resembles a patchwork quilt with polycrystals of different orientation and size separated by grain boundaries forming a mosaic. These structures play an influential role in determining the transport and optical properties of the membrane.

Yin
et al.

(p.
488
; see the Perspective by

Neshev and Kivshar

) demonstrate a simple microscopy technique based on the nonlinear optical response of the materials to probe and characterize atomically thin layers of MoS
2
. The technique should prove useful during the characterization and optimization of atomically thin membranes.
Greater Sensitivity to Drought Accompanies Maize Yield Increase in the U.S. Midwest
Authors: Lobell David B. , Roberts Michael J. , Schlenker Wolfram , Braun Noah , Little Bertis B. , Rejesus Roderick M. , Hammer Graeme L.
Published: May 2014

Predicting Responses to Drought

The U.S. Corn Belt accounts for a sizeable portion of the world's maize growth. Various influences have increased yields over the years.

Lobell
et al.

(p.
516
; see the Perspective by

Ort and Long

) now show that sensitivity to drought has been increasing as well. It seems that as plants have been bred for increased yield under ideal conditions, the plants become more sensitive to non-ideal conditions. A key factor may be the planting density. Although today's maize varieties are more robust to crowding and the farmer can get more plants in per field, this same crowding takes a toll when water resources are limited.
Tolerance for Predatory Wildlife
Authors: Treves Adrian , Bruskotter Jeremy
Published: May 2014

Can individual tolerance toward predators affect the success of predator conservation?
Dysfunctional Mechanosensing in Aneurysms
Authors: Humphrey Jay D. , Milewicz Dianna M. , Tellides George , Schwartz Martin A.
Published: May 2014

Cellular sensing of a compliant extracellular matrix may be critical in maintaining structural integrity of the aorta.
Limits on Yields in the Corn Belt
Authors: Ort Donald R. , Long Stephen P.
Published: May 2014

Increasing vapor pressure deficit and drought sensitivity will limit future corn yields in the U.S. Midwest.

[Also see Report by

Lobell
et al.

]
A New Wrap for Neuronal Activity?
Authors: Bechler Marie E. , ffrench-Constant Charles
Published: May 2014

Neuron activity alters the state of white matter in the mammalian brain.

[Also see Research Article by

Gibson
et al.

]
The Power of Curiosity
Authors: Turner Michael S.
Published: May 2014

In March of 2014, 47 scientists from 15 institutions (including my own) announced that a South Pole–based microwave telescope had taken us back to a time when the universe was 10
−38
seconds old—when everything that we can see today occupied a space much smaller than that occupied by a proton, and when the energy level of the universe was a trillion times greater than that produced by the world's most powerful accelerator, the Large Hadron Collider in Switzerland. Assuming that this amazing discovery by the Background Imaging of Cosmic Extragalactic Polarization (BICEP2) collaboration is confirmed, this cosmic remnant beats the previous record holder for earliest fossil of our cosmic birth (the helium and deuterium made when the universe was seconds old) by 38 orders of magnitude. Rarely has science advanced by such a giant leap, and it will take us years if not decades to fully comprehend all the implications of this incredible moment in science. Although we are used to cosmology stunning us with beautiful images and mind-stretching discoveries such as dark energy and dark matter, even this cosmologist with almost 40 years of experience was awed and shocked by this big, big find.
Soaring MERS Cases in Saudi Arabia Raise Alarms
Authors: Kupferschmidt Kai
Published: May 2014

A sudden explosion of Middle East respiratory syndrome cases creates pandemic worries, but there's no evidence yet of dangerous mutations.
As Pentagon Downsizes, Budgets Shrink for Academic Research
Authors: Malakoff David
Published: May 2014

Pentagon plans to trim research spending could hit universities hard.
Therapeutic Cloning Reaches Milestone
Authors: Vogel Gretchen
Published: May 2014

Scientists have finally managed to derive patient-specific embryonic stem cells. But the technique still faces practical, ethical, and legal hurdles.
LIFE SCIENCE TECHNOLOGIES: Souping Up Your 'Scope
Authors: May Mike
Published: May 2014

The diversity of options for today's microscopes—objectives and cameras, advanced stages and software, sources of illumination, and more—challenge even the experts when designing a new system. The process gets even more complex when faced with constraints, such as a budget or a specific set of necessary applications. Consequently, life scientists need to know where to spend and when to save. The experts interviewed here provide some pointers and give us insight into some of the newest components in the fast-changing field of microscopy.
Diagnostic Potential of Monoclonal Antibodies Specific to the Unique O-Antigen of Multidrug-Resistant Epidemic Escherichia coli Clone ST131-O25b:H4
Authors: Szijártó Valéria , Lukasiewicz Jolanta , Gozdziewicz Tomasz K. , Magyarics Zoltán , Nagy Eszter , Nagy Gábor
Published: May 2014

TheEscherichia colilineage sequence type 131 (ST131)-O25b:H4 is a globally spread multidrug-resistant clone responsible for a great proportion of extraintestinal infections. Driven by the significant medical needs associated with this successful pathogenic lineage, we generated murine monoclonal antibodies (MAbs) against its lipopolysaccharide (LPS) O25b antigen in order to develop quick diagnostic tests. Murine monoclonal antibodies were generated by immunizing mice with whole killed nonencapsulated ST131-O25bE. colicells and screening hybridoma supernatants for binding to purified LPS molecules obtained from anE. coliST131-O25b clinical isolate. The MAbs selected for further study bound to the surface of liveE. coliO25b strains irrespective of the capsular type expressed, while they did not bind to bacteria or purified LPS from other serotypes, including the related classical O25 antigen (O25a). Using these specific MAbs, we developed a latex bead-based agglutination assay that has greater specificity and is quicker and simpler than the currently available typing methods. The high specificities of these MAbs can be explained by the novel structure of the O25b repeating unit elucidated in this article. Based on comparative analysis by nuclear magnetic resonance (NMR) and mass spectrometry, theN-acetyl-fucose in the O25a O-antigen had been replaced byO-acetyl-rhamnose in the O25b repeating unit. The genetic determinants responsible for this structural variation were identified by aligning the corresponding genetic loci and were confirmed bytrans-complementation of a rough mutant by the subserotype-specific fragments of therfboperons.
Improved Molecular Typing Assay for Rhinovirus Species A, B, and C
Authors: Bochkov Yury A. , Grindle Kristine , Vang Fue , Evans Michael D. , Gern James E.
Published: May 2014

Human rhinoviruses (RVs), comprising three species (A, B, and C) of the genus
Enterovirus
, are responsible for the majority of upper respiratory tract infections and are associated with severe lower respiratory tract illnesses such as pneumonia and asthma exacerbations. High genetic diversity and continuous identification of new types necessitate regular updating of the diagnostic assays for the accurate and comprehensive detection of circulating RVs. Methods for molecular typing based on phylogenetic comparisons of a variable fragment in the 5′ untranslated region were improved to increase assay sensitivity and to eliminate nonspecific amplification of human sequences, which are observed occasionally in clinical samples. A modified set of primers based on new sequence information and improved buffers and enzymes for seminested PCR assays provided higher specificity and sensitivity for virus detection. In addition, new diagnostic primers were designed for unequivocal species and type assignments for RV-C isolates, based on phylogenetic analysis of partial VP4/VP2 coding sequences. The improved assay was evaluated by typing RVs in >3,800 clinical samples. RVs were successfully detected and typed in 99% of the samples that were RV positive in multiplex diagnostic assays.
Comparative Evaluation of the Diagenode Multiplex PCR Assay on the BD Max System versus a Routine In-House Assay for Detection of Bordetella pertussis
Authors: Kenicer Juliet , Hardie Alison , Hamilton Fiona , Gadsby Naomi , Templeton Kate
Published: May 2014

This study looked at 128 nasopharyngeal aspirates (NPA) and 162 throat swabs (TS) tested with the Diagenode multiplex assay on the BD Max system versus our in-house
Bordetella pertussis
PCR. Sensitivity and specificity were 97.3% and 100% for NPA and 88.3% and 98% for TS, respectively. Of positive NPA, 42.1% were coinfected with respiratory viruses.
First Human Case of Fastidiosipila sanguinis Infection
Authors: Beauruelle Clémence , Le Bars Hervé , Pougnet Laurence , Lesecq Ludovic , Buisson Philippe , Héry-Arnaud Geneviève
Published: May 2014

Fastidiosipila sanguinis
is a Gram-positive anaerobic coccus. We report the first case of osteitis implicating this species. The strain was accurately identified by 16S rRNA sequence analysis, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) identification having failed. The reservoir remained unclear; an endogenous origin is suspected.
Emergence of New CMRSA7/USA400 Methicillin-Resistant Staphylococcus aureus
spa
Types in Alberta, Canada, from 2005 to 2012
Authors: Li Vincent , Chui Linda , Simmonds Kimberley , Nguyen Thuha , Golding George R. , Yacoub Wadieh , Ferrato Christina , Louie Marie
Published: May 2014

Methicillin-resistant
Staphylococcus aureus
(MRSA) has become one of the most significant pathogens affecting global public health and health care systems. In Canada and the United States, the spread of MRSA is primarily attributed to a single dominant epidemic clone: CMRSA10/USA300. Despite this, the CMRSA7/USA400 epidemic clone has been reported to be the predominate epidemic clone in several Canadian provinces and some parts of the United States. This study examined the epidemiology of CMRSA7/USA400 MRSA in Alberta, Canada, from June 2005 to December 2012. Molecular characterization of CMRSA7/USA400 isolates was done using
spa
, SCC
mec
, PVL, and PFGE typing and identified two predominant
spa
types in Alberta: t128 and t1787. Although closely related, these
spa
types have distinct geographic distributions. From 2010 to 2012, the number of t128 infections has remained stable while there has been a nearly 3-fold increase in the number of provincial t1787 infections, accompanied by 10-fold increases in t1787 infection rates in some communities. Most t128 and t1787 patients were First Nations or Inuit people, and isolates were usually from skin and soft tissue infections in outpatients. t128 patients were significantly older than t1787 patients. Antimicrobial susceptibility testing showed higher mupirocin resistance in t1787 than in t128 MRSA. Improved strategies to reduce or stabilize t1787 infections in Alberta are needed.
Viral Load Detection Using Dried Blood Spots in a Cohort of HIV-1-Infected Children in Uganda: Correlations with Clinical and Immunological Criteria for Treatment Failure
Authors: Costenaro Paola , Lundin Rebecca , Petrara Maria Raffaella , Penazzato Martina , Massavon William , Kizito Susan , Nabachwa Sandra Monica , Nannyonga Musoke Maria , Namisi Charles , Morelli Erika , Bilardi Davide , Mazza Antonio , Zanchetta Marisa , Giaquinto Carlo , De Rossi Anita
Published: May 2014

Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children in Uganda. Of 104 children on combined antiretroviral treatment (cART), 12.5% experienced clinical and/or immunological failure, while 28.8%, 44.2%, and 26.9% had VLs of <1,000, 1,000 to 5,000, and >5,000 copies/ml, respectively. Clinical/immunological failure poorly predicted virological failure.
Comparison of Rates of Positivity for Bordetella pertussis by Real-Time PCR between Specimens Collected with Rayon Swabs on Aluminum Wire Shaft in Amies Gel with Charcoal and Specimens Collected with Flocked Swabs in Universal Viral Transport Medium during an Epidemic
Authors: Arbefeville Sophie , Ferrieri Patricia
Published: May 2014

A comparison of real-time PCR positivity rates for
Bordetella pertussis
between specimens collected with rayon swabs on an aluminum wire shaft in Amies gel with charcoal and those collected with flocked swabs in universal viral transport medium during an epidemic revealed that their performances were comparable.
Rearrangement of a Large Novel Pseudomonas aeruginosa Gene Island in Strains Isolated from a Patient Developing Ventilator-Associated Pneumonia
Authors: Singh G. , Srinivasan R. , Cheng J. , Peng Z. , Fujimura K. , Baek M. S. , Panzer A. R. , Tringe S. G. , Chen F. , Sorek R. , Weng L. , Bristow J. , Wiener-Kronish J. P. , Lynch S. V.
Published: May 2014

Bacterial gene islands add to the genetic repertoire of opportunistic pathogens. Here, we perform comparative analyses of three
Pseudomonas aeruginosa
strains isolated sequentially over a 3-week period from a patient with ventilator-associated pneumonia (VAP) who received clindamycin and piperacillin-tazobactam as part of their treatment regime. While all three strains appeared to be clonal by standard pulsed-field gel electrophoresis, whole-genome sequencing revealed subtle alterations in the chromosomal organization of the last two strains; specifically, an inversion event within a novel 124-kb gene island (PAGI 12) composed of 137 open reading frames [ORFs]. Predicted ORFs in the island included metabolism and virulence genes. Overexpression of a gene island-borne putative β-lactamase gene was observed following piperacillin-tazobactam exposure and only in those strains that had undergone the inversion event, indicating altered gene regulation following genomic remodeling. Examination of a separate cohort of 76 patients with VAP for integration at this tRNA
lys
recombination site demonstrated that patients exhibiting evidence of integration at this site had significantly higher 28-day mortality. These findings provide evidence that
P. aeruginosa
can integrate, rapidly remodel, and express exogenous genes, which likely contributes to its fitness in a clinical setting.
Development and Application of a Multilocus Sequence Typing Scheme for Streptococcus gallolyticus subsp. gallolyticus
Authors: Dumke J. , Hinse D. , Vollmer T. , Knabbe C. , Dreier J.
Published: May 2014

Streptococcus gallolyticus
subsp.
gallolyticus
(formerly known as
S. bovis
biotype I) is a commensal of the gastrointestinal tract in animals and in up to 15% of healthy humans. Furthermore, it is a facultative pathogen that can cause infectious endocarditis, mastitis, and septicemia. The number of infections is increasing, but the transmission routes and zoonotic potential remain unknown. To assess the zoonotic potential and characterize the epidemiological structure of
S. gallolyticus
subsp.
gallolyticus
, we established a multilocus sequence typing (MLST) scheme. We amplified and sequenced internal fragments of seven housekeeping genes. The resulting sequences were analyzed with BioNumerics software 6.6 by using the unweighted-pair group method using average linkages algorithm. A total of 101
S. gallolyticus
subsp.
gallolyticus
strains isolated from animals, humans, and environmental samples were analyzed and divided into 50 sequence types. Our first results highlight the importance of this MLST scheme for investigating the epidemiology, transmission patterns, and infection chains of
S. gallolyticus
subsp.
gallolyticus
.