bluuebunny/crossref_metadata_2025 huggingface dataset:
Land use patterns skew sex ratios, decrease genetic diversity and trump the effects of recent climate change in an endangered turtle
Authors: Reid Brendan N. , Peery M. Z.
Published: October 2014

Aim

Changes in both land use and climate can cause population declines and species extinctions, but the relative effects of these two stressors are often dependent on species‐specific life histories. Turtles are highly threatened as a taxonomic group and are particularly sensitive to environmental change due to their life history, habitat preferences and physiology. We used both sex data and genetic diversity across a landscape‐scale gradient in land use intensity and recent climate change to characterize the relative effects of these factors on three turtle species (including the endangered Blanding's turtle, Emydoidea blandingii) with different life histories and thus different vulnerabilities to environmental change.

Location

Wisconsin, USA.

Methods

Turtles were captured and sampled for genetic analyses at 18 sites. Sampled individuals were genotyped for species‐specific sets of microsatellite markers, and population‐level genetic diversity was assessed using rarefied allelic richness and heterozygosity. The relative effects of road density, public land area and recent climate change on genetic diversity and sex ratio were evaluated using regression methods and model‐selection criteria.

Results

Increased land use intensity was associated with male‐skewed sex ratios and decreased genetic diversity in E. blandingii but not co‐occurring species. Recent climate change did not explain variability in either sex ratio or genetic diversity for any of the three species examined.

Main conclusions

Changing land use has multiple impacts on turtle populations that are modulated by species‐specific life history traits. Extensive terrestrial movements associated with nesting in E. blandingii increase female vulnerability to road mortality, which in turn has led to declines in genetic diversity. The predicted effects of recent climate change may have been dampened by behavioural plasticity. We suggest that the disproportionate effect of land use on E. blandingii warrants greater legal protection for this species.
Impact of haemophilia with inhibitors on caregiver burden in the United States
Authors: DeKoven M. , Karkare S. , Lee W. C. , Kelley L. A. , Cooper D. L. , Pham H. , Powers J. , Wisniewski T.
Published: October 2014

Inhibitor development complicates haemophilia treatment and may impact caregiver burden. Compare overall burden of caregivers of children with/without inhibitors in the United States using a novel disease‐specific questionnaire and the previously validated CarerQol. An on‐line questionnaire with six burden domains (i.e. emotional stress, personal sacrifice, financial burden, medical management, child's pain, and transportation) and three visual analogue scales (VAS) was developed based upon a targeted literature review and previous survey findings. The study sample consisted of caregivers of children with haemophilia. The total burden score was calculated by summing the six individual burden domain scores. Higher scores represented greater burden. Descriptive statistics was performed to examine the sample characteristics. The Wilcoxon rank‐sum test was performed to compare burden by inhibitor status. All variables were considered significant at P < 0.001. A total of 310 caregivers completed the survey; 30 of them reported caring for a child with an inhibitor. A majority of caregivers of children with inhibitors were mothers (80.0%) and between 35 and 44 years of age (56.7%). Caregivers of children with inhibitors reported significantly higher median total burden scores (99.0 vs. 76.5, P < 0.0001) and median burden‐VAS scores (5.5 vs. 3.0, P < 0.0001), as compared to those caring for children without inhibitors. A similar trend was seen across all the six burden domains, with greatest difference in the median burden scores observed in the ‘personal sacrifice’ (3.2 vs. 2.0) and ‘transportation’ (3.3 vs. 2.3) domains. Burden of caregivers should be considered when assessing the psychosocial aspects of managing patients with inhibitors.
“FUTURE PAST”: TIME AND TELEOLOGY IN (ANCIENT) HISTORIOGRAPHY
Authors: GRETHLEIN JONAS
Published: October 2014

The historian's account of the past is strongly shaped by the future of the events narrated. The telos, that is, the vantage point from which the past is envisaged, influences the selection of the material as well as its arrangement. Although the telos is past for historians and readers, it is future for historical agents. The term “future past,” coined by Reinhart Koselleck to highlight the fact that the future was seen differently before the Sattelzeit, also lends itself to capturing this asymmetry and elucidating its ramifications for the writing of history. The first part of the essay elaborates on the notion of “future past”: besides considering its significance and pitfalls, I offset it against the perspectivity of historical knowledge and the concept of narrative “closure” (I). Then the works of two ancient historians, Polybius and Sallust, serve as test cases that illustrate the intricacies of “future past.” Neither has received much credit for intellectual sophistication in scholarship, and yet the different narrative strategies Polybius and Sallust deploy reveal profound reflections on the temporal dynamics of writing history (II). Although the issue of “future past” is particularly pertinent to the strongly narrative historiography of antiquity, the controversy about the end of the Roman Republic demonstrates that it also applies to the works of modern historians (III). Finally, I will argue that “future past” alerts us to an aspect of how we relate to the past that is in danger of being obliterated in the current debate on “presence” and history. The past is present in customs, relics, and rituals, but the historiographical construction of the past is predicated on a complex hermeneutical operation that involves the choice of a telos. The concept of “future past” also differs from post‐structuralist theories through its emphasis on time. Retrospect calms the flow of time, but is unable to arrest it fully, as the openness of the past survives in the form of “future past” (IV).
THE HOLOCAUST IS OVER?
Authors: Garbarini Alexandra
Published: October 2014

Alon Confino has issued a desideratum to other historians that they should bring questions and insights from cultural history to bear on the study of the Holocaust. Taking the work of Saul Friedländer as his point of departure, Confino nonetheless sets out on a path different from Friedländer's. He turns away from the goal of “integrated history” and instead seeks to investigate the realm of German culture, understood as encompassing much more than just Nazi ideology. By analyzing how the Holocaust has come to be perceived as unprecedented, as a rupture in human history, and furthermore by treating Jewish victims' sense of disbelief as an artifact of the past, one that has continued to inform unduly the historical understanding of the Holocaust up to the present day, historians will be able to account anew for what made the persecution and extermination of Jews imaginable and thus possible. With Confino's approach, a major historiographical question resurfaces, however: namely, what place an analysis of non‐Germans should occupy in the history of the Holocaust, and in particular what place should be accorded to Jewish voices? This essay argues that we cannot make sense of why Germans supported and carried out the Holocaust without also considering Jewish contemporaneous perspectives and imaginings.
WHITHER “WHAT IF” HISTORY?
Authors: Rosenfeld Gavriel D.
Published: October 2014

Richard Evans's new book, Altered Pasts, offers a perceptive but flawed critique of the field of counterfactual history. The author provides a useful historical survey of the field's recent rise to prominence and intelligently analyzes its respective strengths and weaknesses. His overall assessment of the field is quite skeptical, however. Evans cites many reasons for his skepticism, but his overall critique can be summarized in three words: plausibility, politicization, and popularity. Evans faults works of counterfactual history for their frequently implausible narratives, their promotion of political agendas, and their distressing degree of popularity. In advancing his critique, Evans makes many valid observations that call attention to important deficiencies in the field. But his view is a partial one that neglects countervailing evidence and never penetrates to the heart of why the field has left the margins for the mainstream. Evans's study provides a useful introduction to an understudied topic, but further research—ideally of a less partisan nature—is required for us to better understand counterfactual history's increasing appeal.
Effects of Maternal Responsiveness on Infant Responsiveness and Behavior in the Still‐Face Task
Authors: Bigelow Ann E. , Power Michelle
Published: October 2014

The effects of maternal responsiveness on infant responsiveness and behavior in the Still‐Face Task were longitudinally examined through infants' first 3 months. Maternal vocal responsiveness and infant vocal and smiling responsiveness significantly increased when infants were 2 months of age. Mothers showed continuity of individual differences in vocal responsiveness from the infants' newborn period. Maternal responsiveness predicted infant responsiveness within and across sessions. Compared with infants with low‐responsive mothers, infants with high‐responsive mothers were more attentive and affectively engaged during the Still‐Face Task from 1 month of age. Infants with high‐responsive mothers discriminated between the task phases with their smiling at 1 month, a month before infants with low‐responsive mothers did so. Infants in both groups discriminated between the phases with their attention and nondistress vocalizations throughout their first 3 months. Results suggest that maternal responsiveness influences infant responsiveness and facilitates infants' engagement and expectations for social interaction.
Variations of chromosomes 2 and 3 gene expression profiles among pulmonary telocytes, pneumocytes, airway cells, mesenchymal stem cells and lymphocytes
Authors: Zheng Minghuan , Sun Xiaoru , Zhang Miaomiao , Qian Mengjia , Zheng Yonghua , Li Meiyi , Cretoiu Sanda M. , Chen Chengshui , Chen Luonan , Cretoiu Dragos , Popescu Laurentiu M. , Fang Hao , Wang Xiangdong
Published: October 2014

Telocytes (TCs) were identified as a distinct cellular type of the interstitial tissue and defined as cells with extremely long telopodes (Tps). Our previous data demonstrated patterns of mouse TC‐specific gene profiles on chromosome 1. The present study focuses on the identification of characters and patterns of TC‐specific or TC‐dominated gene expression profiles in chromosome 2 and 3, the network of principle genes and potential functional association. We compared gene expression profiles of pulmonary TCs, mesenchymal stem cells, fibroblasts, alveolar type II cells, airway basal cells, proximal airway cells, CD8+T cells from bronchial lymph nodes (T‐BL), and CD8+ T cells from lungs (T‐LL). We identified that 26 or 80 genes of TCs in chromosome 2 and 13 or 59 genes of TCs up‐ or down‐regulated in chromosome 3, as compared with other cells respectively. Obvious overexpression of Myl9 in chromosome 2 of TCs different from other cells, indicates that biological functions of TCs are mainly associated with tissue/organ injury and ageing, while down‐expression of Pltp implies that TCs may be associated with inhibition or reduction of inflammation in the lung. Dominant overexpression of Sh3glb1, Tm4sf1 or Csf1 in chromosome 3 of TCs is mainly associated with tumour promotion in lung cancer, while most down‐expression of Pde5 may be involved in the development of pulmonary fibrosis and other acute and chronic interstitial lung disease.
Protective Effects of Middle School Comprehensive Sex Education With Family Involvement
Authors: Grossman Jennifer M. , Tracy Allison J. , Charmaraman Linda , Ceder Ineke , Erkut Sumru
Published: October 2014

BACKGROUND

School‐based comprehensive sex education programs can reduce early adolescents' risky sexual behavior. The purpose of this study was to assess the effectiveness of a 3‐year comprehensive sex education program in delaying vaginal sex for middle school students and whether the family component of the intervention contributes to its effectiveness.

METHODS

This longitudinal evaluation followed a cohort of 6th graders (N = 2453) through the end of 8th grade. The design used random assignment of 24 schools into treatment and comparison conditions. The analysis included multiple‐group logistic regression to assess differences in delay of sex between intervention and comparison groups.

RESULTS

In schools where the program was taught, 16% fewer boys and 15% fewer girls had had sex by the end of 8th grade compared to boys and girls at comparison schools. Completing family activities during the first year of the program predicted delayed sexual debut for boys.

CONCLUSIONS

Theory‐based, developmentally appropriate, comprehensive sex education programs that include parent involvement can be effective in delaying vaginal sex for middle school students. Parent involvement is particularly important for boys, as family activities may encourage parents to talk with their sons earlier and more frequently.
Physical Activity in Preschool Children: Comparison Between Montessori and Traditional Preschools
Authors: Pate Russell R. , O'Neill Jennifer R. , Byun Wonwoo , McIver Kerry L. , Dowda Marsha , Brown William H.
Published: October 2014

BACKGROUND

Little is known about the influence of Montessori methods on children's physical activity (PA). This cross‐sectional study compared PA of children attending Montessori and traditional preschools.

METHODS

We enrolled 301 children in 9 Montessori and 8 traditional preschools in Columbia, South Carolina. PA was measured by accelerometry on weekdays during preschool (In‐School), non‐school (Non‐School), and all day (All Day). Minutes/hour of light, moderate‐to‐vigorous (MVPA), and total PA (light + MVPA) were calculated.

RESULTS

Children attending Montessori preschools accumulated more In‐School light (7.7 vs. 6.5 minute/hour), MVPA (7.7 versus 6.5 minute/hour), and total PA (15.4 versus 13.0 minute/hour) than children attending traditional preschools, after adjusting for sex, race/ethnicity, body mass index, parent education and neighborhood poverty index. For Non‐School (8.5 versus 6.2 minute/hour) and All Day (8.5 versus 7.6 minute/hour), children in Montessori preschools accumulated more MVPA than children in traditional preschools. In‐School PA was higher for children in private Montessori than public Montessori preschools (8.1 versus 7.0 minute/hour; 8.1 versus 6.7 minute/hour; 16.1 versus 13.6 minute/hour, for light, MVPA, and total PA, respectively).

CONCLUSIONS

Children attending Montessori preschools were more active than children attending traditional preschools. Adopting the Montessori system may be an important strategy for promoting PA in children.
Irrepressible MONOPTEROS/ARF5 promotes de novo shoot formation
Authors: Ckurshumova Wenzislava , Smirnova Tatiana , Marcos Danielle , Zayed Yara , Berleth Thomas
Published: October 2014

In vitro regeneration of complete organisms from diverse cell types is a spectacular property of plant cells. Despite the great importance of plant regeneration for plant breeding and biotechnology, its molecular basis is still largely unclear and many important crop plants have remained recalcitrant to regeneration.

Hormone‐exposure protocols to trigger the de novo formation of either roots or shoots from callus tissue demonstrate the importance of auxin and cytokinin signaling pathways, and genetic differences in these pathways may contribute to the highly divergent responsiveness of plant species to regeneration protocols.

In this study, we show that signaling through MONOPTEROS (MP)/AUXIN RESPONSE FACTOR 5 is necessary for the formation of shoots from Arabidopsis calli. Most strikingly, an irrepressible variant of MP, MPΔ, is sufficient for promoting de novo shoot formation through pathways involving the genetically downstream functions of SHOOT MERISTEMLESS (STM) and CYTOKININ RESPONSE FACTOR2 (CRF2).

We conclude that the MPΔ genotype can promote de novo shoot formation and can be used to probe corresponding signaling pathways.
Beliefs and environmental behavior: The moderating effect of emotional intelligence
Authors: Aguilar‐Luzón Maria Carmen , Calvo‐Salguero Antonia , Salinas Jose Maria
Published: October 2014

Recent decades have seen a proliferation of studies aiming to explain how pro‐environmental behavior is shaped by attitudes, values and beliefs. In this study, we have included an aspect in our analysis that has been rarely touched upon until now, that is, the intelligent use of emotions as a possible component of pro‐environmental behavior. We applied the Trait Meta Mood Scale‐24 (TMMS‐24) and the New Environmental Paradigm scale to a sample of 184 male and female undergraduate students. We also carried out correlation and hierarchical regression analyses of blocks. The results show the interaction effects of the system of environmental beliefs and the dimensions of emotional intelligence on glass recycling attitudes, intentions and behavior. The results are discussed from the perspective of research on how the management of emotions guides thought and behavior.
Influence of protein tyrosine phosphatase gene (PTPN22) polymorphisms on rheumatic heart disease susceptibility in North Indian population
Authors: Gupta U. , Mir S. S. , Chauhan T. , Garg N. , Agarwal S. K. , Pande S. , Mittal B.
Published: October 2014

This study was aimed to assess the association of Protein tyrosine phosphatase non‐receptor22 (PTPN22) gene single nucleotide polymorphisms (SNPs) with rheumatic heart disease (RHD) susceptibility in 400 RHD patients and 300 controls. The PTPN22 polymorphisms (rs2476601, rs1217406 and rs3789609) were genotyped using Taqman probes (Applied Biosystems, Foster City, CA). Statistical analysis was performed by spss and haplotype analysis by snpstat. The frequencies of variant alleles were not different between controls and cases (rs2476601: 2.00% & 1.05%; rs1217406: 36.33% & 34.75%; and rs3789609: 38.17% & 40.00%, respectively]. However, G rs2476601 A rs1217406 T rs3789609 haplotype turned out to be a low risk factor for RHD (P = 0.0042) predisposition in females and adult patients. This study suggests PTPN22 haplotype may modulate the risk to RHD in North Indians.
Simulation of Drug-Loaded Nanoparticles Transport Through Drug Delivery Microchannels
Authors: Ma Yongting , Pidaparti Ramana M.
Published: October 2014

Ocular drug delivery is a complex and challenging process and understanding the transport characteristics of drug-loaded particles is very important for designing safe and effective ocular drug delivery devices. In this paper, we investigated the effect of the microchannel configuration of the microdevice, the size of drug-loaded nanoparticles (NPs), and the pressure gradient of fluid flow in determining the maximum number of NPs within a certain outlet region and transportation time of drug particles. We employed a hybrid computational approach that combines the lattice Boltzmann model for fluids with the Brownian dynamics model for NPs transport. This hybrid approach allows to capture the interactions among the fluids, NPs, and barriers of microchannels. Our results showed that increasing the pressure gradient of fluid flow in a specific type of microchannel configuration (tournament configuration) effectively decreased the maximum number of NPs within a certain outlet region as well as transportation time of the drug loaded NPs. These results have important implications for the design of ocular drug delivery devices. These findings may be particularly helpful in developing design and transport optimization guidelines related to creating novel microchannel configurations for ocular drug delivery devices.
Discharge Coefficients in Aerostatic Bearings With Inherent Orifice-Type Restrictors
Authors: Chang S. H. , Chan C. W. , Jeng Y. R.
Published: October 2014

In aerostatic bearing analysis, determining film pressure by solving the Reynolds equation in a numerical model is more effective than conducting bearing experiments or performing computational fluid dynamics (CFD) simulations. However, the discharge coefficient of an orifice-type restrictor is generally a given number that dominates model accuracy. This study investigated the influence of geometry and flow parameters on this discharge coefficient. The results indicate that this discharge coefficient is sensitive to the orifice diameter and film thickness and that the effects of the supply pressure, bearing radius, supply orifice length, supply passage diameter, conicity depth, and conicity angle can be disregarded. This study also built a surrogate model of this discharge coefficient based on the orifice diameter and film thickness by using artificial neural networks (ANNs).
Nonlinear Pitch Decay Motion of a Floating Offshore Wind Turbine Structure
Authors: Thiagarajan K. P. , Urbina R. , Hsu W.
Published: October 2014

Model tests were conducted on three generic floating wind turbine systems in 2011 and reported in a series of papers at the 31st Ocean, Offshore, and Arctic Engineering Conference in 2012. These tests were conducted at the MARIN facility in The Netherlands, by a consortium of universities, government research organizations, and industry. As part of the testing program, decay tests in platform pitch were conducted with and without wind forcing. It was found that for spar and semisubmersible type structures, resonant pitch motion was damped due to wind in storm sea conditions. The nonlinear decay motion of a floating wind turbine platform is modeled using a one degree-of-freedom nonlinear oscillation equation about a mean offset angle. Attention is paid to the turbine thrust coefficient and its variability with respect to oncoming flow speed, which in turn is affected by the structure pitch motion. The equation of motion reveals that the mean offset position has an important role in the stiffness, damping, and consequently the natural period of pitch motion. Several important dimensionless parameters are introduced. The paper discusses a simple thrust model for an offshore wind turbine (OWT) based on rudiments of blade element theory. Using the simplified thrust coefficient formulation, the increase in platform pitch damping due to wind is formulated. Experimental data reported from prior tests described above show good agreement with the theoretical model.
A nonrigid registration method for correcting brain deformation induced by tumor resection
Authors: Liu Yixun , Yao Chengjun , Drakopoulos Fotis , Wu Jinsong , Zhou Liangfu , Chrisochoides Nikos
Published: October 2014

Purpose:

This paper presents a nonrigid registration method to align preoperative MRI with intraoperative MRI to compensate for brain deformation during tumor resection. This method extends traditional point‐based nonrigid registration in two aspects: (1) allow the input data to be incomplete and (2) simulate the underlying deformation with a heterogeneous biomechanical model.

Methods:

The method formulates the registration as a three‐variable (point correspondence, deformation field, and resection region) functional minimization problem, in which point correspondence is represented by a fuzzy assign matrix; Deformation field is represented by a piecewise linear function regularized by the strain energy of a heterogeneous biomechanical model; and resection region is represented by a maximal simply connected tetrahedral mesh. A nested expectation and maximization framework is developed to simultaneously resolve these three variables.

Results:

To evaluate this method, the authors conducted experiments on both synthetic data and clinical MRI data. The synthetic experiment confirmed their hypothesis that the removal of additional elements from the biomechanical model can improve the accuracy of the registration. The clinical MRI experiments on 25 patients showed that the proposed method outperforms the ITK implementation of a physics‐based nonrigid registration method. The proposed method improves the accuracy by 2.88 mm on average when the error is measured by a robust Hausdorff distance metric on Canny edge points, and improves the accuracy by 1.56 mm on average when the error is measured by six anatomical points.

Conclusions:

The proposed method can effectively correct brain deformation induced by tumor resection.
Colloidal nanoparticles as advanced biological sensors
Authors: Howes Philip D. , Chandrawati Rona , Stevens Molly M.
Published: October 2014

Biological sensing using nanoparticles

Colloidal fluorescent and plasmonic nanoparticles yield intense responses to incident light, making them useful as sensors or probes for sensitive detection in solution. Howes
et al.
review the potential uses of nanoparticle biosensors in research and diagnostics. A range of methods allow for the chemical modification of the particle surfaces so that they can be tuned for specific analytes and give optical signals for a range of biological conditions of interest. Signals can be detected in complex media or in vivo making the particles of interest for both laboratory research and in clinical settings.

Science
, this issue
10.1126/science.1247390
Ubiquitylome analysis identifies dysregulation of effector substrates in SPOP-mutant prostate cancer
Authors: Theurillat Jean-Philippe P. , Udeshi Namrata D. , Errington Wesley J. , Svinkina Tanya , Baca Sylvan C. , Pop Marius , Wild Peter J. , Blattner Mirjam , Groner Anna C. , Rubin Mark A. , Moch Holger , Privé Gilbert G. , Carr Steven A. , Garraway Levi A.
Published: October 2014

Mutant protein in tumors hits the DEK

Cancer genome sequencing projects have uncovered a multitude of mutations in human tumors. Understanding whether and how these mutations contribute to tumor development and progression could ultimately lead to new therapies. Theurillat
et al.
studied the protein product of a gene that is recurrently mutated in prostate cancer. Normally this protein helps attach a biochemical tag to cellular proteins that marks them for degradation. The new work shows that the tumor-associated mutant protein loses this tagging ability, which results in the stabilization of a handful of cellular proteins that would otherwise be degraded. One of the most intriguing of these proteins was DEK, which helps prostate cancer cells invade into surrounding tissue.

Science
, this issue p.
85
The early spread and epidemic ignition of HIV-1 in human populations
Authors: Faria Nuno R. , Rambaut Andrew , Suchard Marc A. , Baele Guy , Bedford Trevor , Ward Melissa J. , Tatem Andrew J. , Sousa João D. , Arinaminpathy Nimalan , Pépin Jacques , Posada David , Peeters Martine , Pybus Oliver G. , Lemey Philippe
Published: October 2014

The hidden history of the HIV pandemic

Rail and river transport in 1960s Congo, combined with the sexual revolution and changes in health care practices, primed the HIV pandemic. Faria
et al.
unpick the circumstances surrounding the ascendancy of HIV from its origins before 1920 in chimpanzee hunters in the Cameroon to amplification in Kinshasa. Around 1960, rail links promoted the spread of the virus to mining areas in southeastern Congo and beyond. Ultimately, HIV crossed the Atlantic in Haitian teachers returning home. From those early events, a pandemic was born.

Science
, this issue p.
56
Altered sterol composition renders yeast thermotolerant
Authors: Caspeta Luis , Chen Yun , Ghiaci Payam , Feizi Amir , Buskov Steen , Hallström Björn M. , Petranovic Dina , Nielsen Jens
Published: October 2014

Tricks for boosting yeast's ethanol yields

To become a widely used source of fuel, widespread industrial production of ethanol using yeast needs to be simple and efficient. However, two conditions ideal for boosting production—tolerance of higher temperatures and high concentrations of ethanol—have been limiting (see the Perspective by Cheng and Kao). Now, Caspetaet al.have used adaptive laboratory evolution to find yeast strains that can tolerate high temperatures and Lamet al.have identified a route to improve yeast's resistance to high concentrations of ethanol.

Science, this issue p.75, p.71; see also p.35
Hot molecules—off the beaten path
Authors: Suits Arthur G. , Parker David H.
Published: October 2014

Highly excited carbon dioxide dissociates unexpectedly to form molecular oxygen

[Also see Report by

Lu
et al.

]
How to survive being hot and inebriated
Authors: Cheng Clint , Kao Katy C.
Published: October 2014

Cell membrane integrity and composition are key to making yeast a better biocatalyst

[Also see Reports by

Lam
et al.

and

Caspeta
et al.

]
Building agricultural research
Authors: Kennedy Donald
Published: October 2014

Nine billion people are expected to inhabit Planet Earth by 2050. Without agricultural research, there is little hope of sustaining this population surge, given that arable land and water supplies are fixed commodities. Yet for decades the agricultural sector has suffered from neglect. If we want to combat new strains of pests that destroy crops, find new crop varieties enriched in nutritional value, improve yields, develop resistance to disease and drought, and provide environmentally sensitive cultivation practices, then agricultural research must be a priority. Why isn't it?
Double-whammy tsunami?
Authors: Pease Roland
Published: October 2014

Japan's 2011 quake may have had a hidden accomplice.
Intruder from the Oort cloud will graze Mars
Authors: Hand Eric
Published: October 2014

Five spacecraft will have front-row seat for the encounter with comet Siding Spring.
Population-Based Epidemiology and Microbiology of Community-Onset Bloodstream Infections
Authors: Laupland Kevin B. , Church Deirdre L.
Published: October 2014

Bloodstream infection (BSI) is a major cause of infectious disease morbidity and mortality worldwide. While a positive blood culture is mandatory for establishment of the presence of a BSI, there are a number of determinants that must be considered for establishment of this entity. Community-onset BSIs are those that occur in outpatients or are first identified <48 h after admission to hospital, and they may be subclassified further as health care associated, when they occur in patients with significant prior health care exposure, or community associated, in other cases. The most common causes of community-onset BSI include
Escherichia coli
,
Staphylococcus aureus
, and
Streptococcus pneumoniae
. Antimicrobial-resistant organisms, including methicillin-resistant
Staphylococcus aureus
and extended-spectrum β-lactamase/metallo-β-lactamase/carbapenemase-producing
Enterobacteriaceae
, have emerged as important etiologies of community-onset BSI.
Microbiological Features and Clinical Relevance of New Species of the Genus Mycobacterium
Authors: Tortoli Enrico
Published: October 2014

Nontuberculous mycobacteria (NTM) are present in the environment, mainly in water, and are occasionally responsible for opportunistic infections in humans. Despite the fact that NTM are characterized by a moderate pathogenicity, the diseases caused by NTM at various body sites are increasing on a worldwide level. Among over 150 officially recognized NTM species, only two or three dozen are familiar to clinicians, and even to most microbiologists. In this paper, approximately 50 new species described in the last 8 years are reviewed, and their role in human infections is assessed on the basis of reported clinical cases. The small number of reports concerning most of the “new” mycobacterial species is responsible for the widespread conviction that they are very rare. Their role is actually largely underestimated, mainly because they often remain unrecognized and misidentified. Aiming to minimize such bias, emphasis has been placed on more common identification pitfalls. Together with new NTM, new members of theMycobacterium tuberculosiscomplex described in the last few years are also an object of the present review.
Pathogenesis of Human Diffusely Adhering Escherichia coli Expressing Afa/Dr Adhesins (Afa/Dr DAEC): Current Insights and Future Challenges
Authors: Servin Alain L.
Published: October 2014

The pathogenicity and clinical pertinence of diffusely adheringEscherichia coliexpressing the Afa/Dr adhesins (Afa/Dr DAEC) in urinary tract infections (UTIs) and pregnancy complications are well established. In contrast, the implication of intestinal Afa/Dr DAEC in diarrhea is still under debate. These strains are age dependently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strains in children and adult. This comprehensive review analyzes the epidemiology and diagnosis and highlights recent progress which has improved the understanding of Afa/Dr DAEC pathogenesis. Here, I summarize the roles of Afa/Dr DAEC virulence factors, including Afa/Dr adhesins, flagella, Sat toxin, andpksisland products, in the development of specific mechanisms of pathogenicity. In intestinal epithelial polarized cells, the Afa/Dr adhesins trigger cell membrane receptor clustering and activation of the linked cell signaling pathways, promote structural and functional cell lesions and injuries in intestinal barrier, induce proinflammatory responses, create angiogenesis, instigate epithelial-mesenchymal transition-like events, and lead topks-dependent DNA damage. UTI-associated Afa/Dr DAEC strains, following adhesin-membrane receptor cell interactions and activation of associated lipid raft-dependent cell signaling pathways, internalize in a microtubule-dependent manner within urinary tract epithelial cells, develop a particular intracellular lifestyle, and trigger a toxin-dependent cell detachment. In response to Afa/Dr DAEC infection, the host epithelial cells generate antibacterial defense responses. Finally, I discuss a hypothetical role of intestinal Afa/Dr DAEC strains that can act as “silent pathogens” with the capacity to emerge as “pathobionts” for the development of inflammatory bowel disease and intestinal carcinogenesis.
Emerging and Reemerging Neglected Tropical Diseases: a Review of Key Characteristics, Risk Factors, and the Policy and Innovation Environment
Authors: Mackey Tim K. , Liang Bryan A. , Cuomo Raphael , Hafen Ryan , Brouwer Kimberly C. , Lee Daniel E.
Published: October 2014

In global health, critical challenges have arisen from infectious diseases, including the emergence and reemergence of old and new infectious diseases. Emergence and reemergence are accelerated by rapid human development, including numerous changes in demographics, populations, and the environment. This has also led to zoonoses in the changing human-animal ecosystem, which are impacted by a growing globalized society where pathogens do not recognize geopolitical borders. Within this context, neglected tropical infectious diseases have historically lacked adequate attention in international public health efforts, leading to insufficient prevention and treatment options. This subset of 17 infectious tropical diseases disproportionately impacts the world's poorest, represents a significant and underappreciated global disease burden, and is a major barrier to development efforts to alleviate poverty and improve human health. Neglected tropical diseases that are also categorized as emerging or reemerging infectious diseases are an even more serious threat and have not been adequately examined or discussed in terms of their unique risk characteristics. This review sets out to identify emerging and reemerging neglected tropical diseases and explore the policy and innovation environment that could hamper or enable control efforts. Through this examination, we hope to raise awareness and guide potential approaches to addressing this global health concern.
Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion
Authors: Dando Samantha J. , Mackay-Sim Alan , Norton Robert , Currie Bart J. , St. John James A. , Ekberg Jenny A. K. , Batzloff Michael , Ulett Glen C. , Beacham Ifor R.
Published: October 2014

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection withBurkholderia pseudomalleican result in melioidosis encephalomyelitis.
IP-10 and MIG Are Compartmentalized at the Site of Disease during Pleural and Meningeal Tuberculosis and Are Decreased after Antituberculosis Treatment
Authors: Yang Qianting , Cai Yi , Zhao Wei , Wu Fan , Zhang Mingxia , Luo Kai , Zhang Yan , Liu Haiying , Zhou Boping , Kornfeld Hardy , Chen Xinchun
Published: October 2014

The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 and MIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC = 0.87 for IP-10 and 0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC = 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-γ) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN-γ release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion and meningitis caused by TB from those of non-TB origins.
Phenotypic and Genotypic Analysis of Clostridium difficile Isolates: a Single-Center Study
Authors: Zhou Yanjiao , Burnham Carey-Ann D. , Hink Tiffany , Chen Lei , Shaikh Nurmohammad , Wollam Aye , Sodergren Erica , Weinstock George M. , Tarr Phillip I. , Dubberke Erik R.
Published: October 2014

Clostridium difficile
infections (CDI) are a growing concern in North America, because of their increasing incidence and severity. Using integrated approaches, we correlated pathogen genotypes and host clinical characteristics for 46
C. difficile
infections in a tertiary care medical center during a 6-month interval from January to June 2010. Multilocus sequence typing (MLST) demonstrated 21 known and 2 novel sequence types (STs), suggesting that the institution's
C. difficile
strains are genetically diverse. ST-1 (which corresponds to pulsed-field gel electrophoresis strain type NAP1/ribotype 027) was the most prevalent (32.6%); 43.5% of the isolates were binary toxin gene positive, of which 75% were ST-1. All strains were ciprofloxacin resistant and metronidazole susceptible, and 8.3% and 13.0% of the isolates were resistant to clindamycin and tetracycline, respectively. The corresponding resistance loci, including potential novel mutations, were identified from the whole-genome sequencing (WGS) of the resistant strains. Core genome single nucleotide polymorphisms (SNPs) determining the phylogenetic relatedness of the 46 strains recapitulated MLST types and provided greater interstrain differentiation. The disease severity was greatest in patients infected with ST-1 and/or binary gene-positive strains, but genome-wide SNP analysis failed to provide additional associations with CDI severity within the same STs. We conclude that MLST and core genome SNP typing result in the same phylogenetic grouping of the 46
C. difficile
strains collected in a single hospital. WGS also has the capacity to differentiate those strains within STs and allows the comparison of strains at the individual gene level and at the whole-genome level.
Chronic Hepatitis E Virus Infection in a Pediatric Female Liver Transplant Recipient
Authors: Passos-Castilho Ana Maria , Porta Gilda , Miura Irene K. , Pugliese Renata P. S. , Danesi Vera L. B. , Porta Adriana , Guimarães Teresa , Seda João , Antunes Eduardo , Granato Celso F. H.
Published: October 2014

We describe a case of chronic hepatitis E virus (HEV) infection in a 13-year-old female liver transplant recipient with recurrent increased aminotransferase levels and acute cellular rejection. This finding demonstrates that chronic HEV infection can occur and should be further investigated in immunocompromised patients in Latin America.
Expression of the Human Cytomegalovirus UL11 Glycoprotein in Viral Infection and Evaluation of Its Effect on Virus-Specific CD8 T Cells
Authors: Gabaev Ildar , Elbasani Endrit , Ameres Stefanie , Steinbrück Lars , Stanton Richard , Döring Marius , Lenac Rovis Tihana , Kalinke Ulrich , Jonjic Stipan , Moosmann Andreas , Messerle Martin
Published: October 2014

The human cytomegalovirus (CMV) UL11 open reading frame (ORF) encodes a putative type I transmembrane glycoprotein which displays remarkable amino acid sequence variability among different CMV isolates, suggesting that it represents an important virulence factor. In a previous study, we have shown that UL11 can interact with the cellular receptor tyrosine phosphatase CD45, which has a central role for signal transduction in T cells, and treatment of T cells with large amounts of a soluble UL11 protein inhibited their proliferation. In order to analyze UL11 expression in CMV-infected cells, we constructed CMV recombinants whose genomes either encode tagged UL11 versions or carry a stop mutation in the UL11 ORF. Moreover, we examined whether UL11 affects the function of virus-specific cytotoxic T lymphocytes (CTLs). We found that the UL11 ORF gives rise to several proteins due to both posttranslational modification and alternative translation initiation sites. Biotin labeling of surface proteins on infected cells indicated that only highly glycosylated UL11 forms are present at the plasma membrane, whereas less glycosylated UL11 forms were found in the endoplasmic reticulum. We did not find evidence of UL11 cleavage or secretion of a soluble UL11 version. Cocultivation of CTLs recognizing different CMV epitopes with fibroblasts infected with a UL11 deletion mutant or the parental strain revealed that under the conditions applied UL11 did not influence the activation of CMV-specific CD8 T cells. For further studies, we propose to investigate the interaction of UL11 with CD45 and the functional consequences in other immune cells expressing CD45.

IMPORTANCE
Human cytomegalovirus (CMV) belongs to those viruses that extensively interfere with the host immune response, yet the precise function of many putative immunomodulatory CMV proteins remains elusive. Previously, we have shown that the CMV UL11 protein interacts with the leukocyte common antigen CD45, a cellular receptor tyrosine phosphatase with a central role for signal transduction in T cells. Here, we examined the proteins expressed by the UL11 gene in CMV-infected cells and found that at least one form of UL11 is present at the cell surface, enabling it to interact with CD45 on immune cells. Surprisingly, CMV-expressed UL11 did not affect the activity of virus-specific CD8 T cells. This finding warrants investigation of the impact of UL11 on CD45 functions in other leukocyte subpopulations.
A Combination of HA and PA Mutations Enhances Virulence in a Mouse-Adapted H6N6 Influenza A Virus
Authors: Tan Likai , Su Shuo , Smith David K. , He Shuyi , Zheng Yun , Shao Zhenwen , Ma Jun , Zhu Huachen , Zhang Guihong
Published: October 2014

H6N6 viruses are commonly isolated from domestic ducks, and avian-to-swine transmissions of H6N6 viruses have been detected in China. Whether subsequent adaptation of H6N6 viruses in mammals would increase their pathogenicity toward humans is not known. To address this, we generated a mouse-adapted (MA) swine influenza H6N6 virus (A/swine/Guangdong/K6/2010 [GDK6-MA]) which exhibited greater virulence than the wild-type virus (GDK6). Amino acid substitutions in PB2 (E627K), PA (I38M), and hemagglutinin ([HA] L111F, H156N, and S263R) occurred in GDK6-MA. HA with the H156N mutation [HA(H156N)] resulted in enlarged plaque sizes on MDCK cells and enhanced early-stage viral replication in mammalian cells. PA(I38M) raised polymerase activity
in vitro
but did not change virus replication in either mammalian cells or mice. These single substitutions had only limited effects on virulence; however, a combination of HA(H156N S263R) with PA(I38M) in the GDK6 backbone led to a significantly more virulent variant. This suggests that these substitutions can compensate for the lack of PB2(627K) and modulate virulence, revealing a new determinant of pathogenicity for H6N6 viruses in mice, which might also pose a threat to human health.

IMPORTANCE
Avian H6N6 influenza viruses are enzootic in domestic ducks and have been detected in swine in China. Infections of mammals by H6N6 viruses raise the possibility of viral adaptation and increasing pathogenicity in the new hosts. To examine the molecular mechanisms of adaptation, a mouse-adapted avian-origin swine influenza H6N6 virus (GDK6-MA), which had higher virulence than its parental virus, was generated. Specific mutations were found in PB2 (E627K), PA (I38M), and HA (L111F, H156N, and S263R) and were assessed for their virulence in mice. The combination of HA(H156N S263R) and PA(I38M) compensated for the lack of PB2(627K) and showed increased pathogenicity in mice, revealing a novel mechanism that can affect the virulence of influenza viruses. H6N6 viruses should be monitored in the field for more virulent forms that could threaten human health.