bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrocarbon contamination and plant species determine the phylogenetic and functional diversity of endophytic degrading bacteria
Authors: Oliveira Vanessa , Gomes Newton C. M. , Almeida Adelaide , Silva Artur M. S. , Simões Mário M. Q. , Smalla Kornelia , Cunha Ângela
Published: October 2013

Salt marsh sediments are sinks for various anthropogenic contaminants, giving rise to significant environmental concern. The process of salt marsh plant survival in such environment is very intriguing and at the same time poorly understood. The plant–microbe interactions may play a key role in the process of environment and in planta detoxification. In this study, a combination of culture‐dependent and culture‐independent molecular approaches [enrichment cultures, polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), DNA sequencing] were used to investigate the effect of petroleum hydrocarbons (PH) contamination on the structure and function [polycyclic aromatic hydrocarbon (PAH) dioxygenase genes] of endophytic bacterial communities of salt marsh plant species (Halimione portulacoides and Sarcocornia perennis) in the estuarine system Ria de Aveiro (Portugal). Pseudomonads dominated the cultivable fraction of the endophytic communities in the enrichment cultures. In a set of fifty isolates tested, nine were positive for genes encoding for PAH dioxygenases (nahAc) and four were positive for plasmid carrying genes encoding PAH degradation enzymes (nahAc). Interestingly, these plasmids were only detected in isolates from most severely PH‐polluted sites. The results revealed site‐specific effects on endophytic communities, related to the level of PH contamination in the sediment, and plant‐species‐specific ‘imprints’ in community structure and in genes encoding for PAH dioxygenases. These results suggest a potential ecological role of bacterial plant symbiosis in the process of plant colonization in urban estuarine areas exposed to PH contamination.
Using genomic tools to maintain diversity and fitness in conservation programmes
Authors: de Cara María Ángeles Rodríguez , Villanueva Beatriz , Toro Miguel Ángel , Fernández Jesús
Published: October 2013

Conservation programmes aim at maximizing the survival probability of populations, by minimizing the loss of genetic diversity, which allows populations to adapt to changes, and controlling inbreeding increases. The best known strategy to achieve these goals is optimizing the contributions of the parents to minimize global coancestry in their offspring. Results on neutral scenarios showed that management based on molecular coancestry could maintain more diversity than management based on genealogical coancestry when a large number of markers were available. However, if the population has deleterious mutations, managing using optimal contributions can lead to a decrease in fitness, especially using molecular coancestry, because both beneficial and harmful alleles are maintained, compromising the long‐term viability of the population. We introduce here two strategies to avoid this problem: The first one uses molecular coancestry calculated removing markers with low minor allele frequencies, as they could be linked to selected loci. The second one uses a coancestry based on segments of identity by descent, which measures the proportion of genome segments shared by two individuals because of a common ancestor. We compare these strategies under two contrasting mutational models of fitness effects, one assuming many mutations of small effect and another with few mutations of large effect. Using markers at intermediate frequencies maintains a larger fitness than using all markers, but leads to maintaining less diversity. Using the segment‐based coancestry provides a compromise solution between maintaining diversity and fitness, especially when the population has some inbreeding load.
Detecting adaptive trait loci in nonmodel systems: divergence or admixture mapping?
Authors: Crawford Jacob E. , Nielsen Rasmus
Published: October 2013

Mapping adaptive trait loci (ATL) underlying ecological divergence is an essential step towards understanding the processes that generate phenotypic diversity. Technological advances have made it possible to sequence exomes in nonmodel systems, providing an efficient means of analysing functional genetic variants. Divergence scans of genetic markers for outlier loci, or ‘divergence mapping’, have been used to map locally adapted genes, but this approach is likely to be underpowered when background divergence is elevated. Genotype–phenotype association tests in admixed populations, or ‘admixture mapping’, may provide a useful approach for mapping locally adapted loci when neutral divergence is high. To determine the power and limits of divergence mapping, we simulated exomes containing a single ATL across two parental populations of varying neutral divergence, estimated divergence and quantified the power to identify the ATL. We found that divergence mapping had very high power when background FST is <0.2, but decreased dramatically above this level. To evaluate the utility of admixture mapping, we simulated exomes from admixed populations, then simulated phenotypes, conducted genotype–phenotype association tests and found that even two generations of random mating after admixture could provide high mapping power in scenarios where pure divergence mapping was ineffective (FST = 0.35). Moreover, admixture mapping had high power across all levels of divergence after 20 generations since admixture. Together with high‐throughput exome sequencing, admixture mapping could be used to map ATL in systems such as Heliconius butterflies or Gryllus crickets when experimental design and analytical approach are chosen accordingly.
Interactions of bacterial flagellar chaperone–substrate complexes with FlhA contribute to co‐ordinating assembly of the flagellar filament
Authors: Kinoshita Miki , Hara Noritaka , Imada Katsumi , Namba Keiichi , Minamino Tohru
Published: October 2013

Assembly of the bacterial flagellar filament is strictly sequential; the junction proteins, FlgK and FlgL, are assembled at the distal end of the hook prior to the FliD cap, which supports assembly of as many as 30 000 FliC molecules into the filament. Export of these proteins requires assistance of flagellar chaperones: FlgN for FlgK and FlgL, FliT for FliD and FliS for FliC. The C‐terminal cytoplasmic domain of FlhA (FlhAC), a membrane component of the export apparatus, provides a binding‐site for these chaperone–substrate complexes but it remains unknown how it co‐ordinates flagellar protein export. Here, we report that the highly conserved hydrophobic dimple of FlhAC is involved in the export of FlgK, FlgL, FliD and FliC but not in proteins responsible for the structure and assembly of the hook, and that the binding affinity of FlhAC for the FlgN/FlgK complex is slightly higher than that for the FliT/FliD complex and about 14‐fold higher than that for the FliS/FliC complex, leading to the proposal that the different binding affinities of FlhAC for these chaperone/substrate complexes may confer an advantage for the efficient formation of the junction and cap structures at the tip of the hook prior to filament formation.
Clinical, radiological, histological and molecular characteristics of paediatric epithelioid glioblastoma
Authors: Broniscer A. , Tatevossian R. G. , Sabin N. D. , Klimo P. , Dalton J. , Lee R. , Gajjar A. , Ellison D. W.
Published: October 2013

Aims

A few case series in adults have described the characteristics of epithelioid glioblastoma (e‐GB), one of the rarest variants of this cancer. We evaluated clinical, radiological, histological and molecular characteristics in the largest series to date of paediatric e‐GB.

Methods

Review of clinical characteristics and therapy, imaging studies and histology was performed in patients younger than 22 years with e‐GB seen at our institution over 15 years. Sequencing of hotspot mutations and fluorescence in situ hybridization of relevant genes were undertaken.

Results

Median age at diagnosis of six patients was 7.6 years. Tumours originated in the cerebral cortex (n = 2) or diencephalon (n = 4). Three patients presented with acute, massive haemorrhage and three had leptomeningeal dissemination at diagnosis. Paediatric e‐GB had the typical histological characteristics seen in adult tumours. Universal immunoreactivity for INI1 and lack of diverse protein expression were seen in all cases. One tumour had a chromosome 22q loss. Three tumours (50%) harboured a BRAF: p.V600E. One thalamic tumour had an H3F3A p.K27M. All patients received radiation therapy with (n = 3) or without chemotherapy (n = 3). All patients experienced tumour progression with a median survival of 169 days. One patient with nonmetastatic disease had early leptomeningeal progression. Two patients had symptomatic tumour spread outside the central nervous system (CNS) through a ventriculoperitoneal shunt. One additional patient had widespread metastases outside the CNS identified at autopsy.

Conclusions

Paediatric e‐GBs are rare cancers with an aggressive behaviour that share histological and genetic characteristics with their adult counterparts. BRAF inhibition is a potential treatment for these tumours.
Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma
Authors: Simpson R. Mark , Bastian Boris C. , Michael Helen T. , Webster Joshua D. , Prasad Manju L. , Conway Catherine M. , Prieto Victor M. , Gary Joy M. , Goldschmidt Michael H. , Esplin D. Glen , Smedley Rebecca C. , Piris Adriano , Meuten Donald J. , Kiupel Matti , Lee Chyi‐Chia R. , Ward Jerrold M. , Dwyer Jennifer E. , Davis Barbara J. , Anver Miriam R. , Molinolo Alfredo A. , Hoover Shelley B. , Rodriguez‐Canales Jaime , Hewitt Stephen M.
Published: October 2013

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun‐exposed sites. Most occur in the oral cavity, with a subset having intra‐epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ‐line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c‐kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model.
Nuclear Diversion Theory and Legitimacy Crisis: The Case of Iran
Authors: Abulof Uriel
Published: October 2013

Can an insecure regime use nuclear diversion to address its eroding domestic legitimacy? This article argues that facing a domestic legitimacy crisis, a regime might opt to “rally round the nuclear flag” to survive. Theoretically, I argue that, compared with conventional diversion, nuclear diversion is less susceptible to structural restraints, has a unique symbolic value that could aid in coping with an acute legitimacy crisis, and spans a host of diversionary strategies as it ascends the escalation ladder, both before and after acquiring the bomb. The theory is examined empirically via Iranian nuclear policy. I argue that facing a deepening legitimacy crisis, the Iranian regime, throughout Ahmadinejad's tenure, has been increasingly drawing on nuclear diversion to boost public support and that, if the legitimacy crisis lingers, the regime may opt to further employ diversionary nuclear strategies, most of which require a viable “nuclear latency,” rather than actual military nuclear capability.

Related Articles

Ripberger, Joseph T., Thomas M. Rabovsky, and Kerry G. Herron. 2011. “.” Politics & Policy 39 (): 891‐923. http://onlinelibrary.wiley.com/doi/10.1111/j.1747‐1346.2011.00327.x/abstract

Kane, John, and Haig Patapan. 2010. “.” Politics & Policy 38 (): 589‐610. http://onlinelibrary.wiley.com/doi/10.1111/j.1747‐1346.2010.00250.x/abstract

Darvich, Djamchid, and W. R. Campbell. 1982. “.” Southeastern Political Review 10 (): 37‐87. http://onlinelibrary.wiley.com/doi/10.1111/j.1747‐1346.1982.tb00034.x/abstract

Related Media

Kurzman, Charles. 2009. “.” . July 18. http://chronicle.com/article/Social‐Science‐on‐Trial‐in‐/48949/

. 2011. “.” . February 24. http://www.bbc.co.uk/news/world‐africa‐12570279
Spontaneous loss of Yr2 avirulence in two lineages of Puccinia striiformis did not affect pathogen fitness
Authors: Sørensen C. K. , Justesen A. F. , Hovmøller M. S.
Published: October 2013

Fitness costs associated with the emergence of virulence (loss of avirulence) have been a subject of much debate in plant pathology. Here, differences in fitness between two pairs of wild types and spontaneous virulence mutants in Puccinia striiformis were studied. The mutants differed from their respective wild types in virulence corresponding to the Yr2 resistance gene in wheat. The wildtype and mutant pairs represented different genetic lineages and virulence phenotypes. Colony size, latent period, lesion growth rate and uredinium density and size were assessed on susceptible and Yr2 resistant wheat varieties. No significant difference was observed for any of the evaluated parameters within wildtype and mutant pairs, i.e. the results did not support a hypothesis of a fitness cost for acquiring virulence in P. striiformis. In contrast, significant differences were found for most of the parameters when isolates were compared according to genetic lineage, which confirm that the applied methodologies were appropriate for detecting differences in pathogen fitness.
An Algorithm for the Estimation of Gestational Age at the Time of Fetal Death
Authors: Conway Deborah L. , Hansen Nellie I. , Dudley Donald J. , Parker Corette B. , Reddy Uma M. , Silver Robert M. , Bukowski Radek , Pinar Halit , Stoll Barbara J. , Varner Michael W. , Saade George R. , Hogue Carol , Willinger Marian , Coustan Donald , Koch Matthew A. , Goldenberg Robert L. ,   Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network
Published: October 2013

Background

Accurate assignment of gestational age (GA) at time of fetal death is important for research and clinical practice. An algorithm to estimate GA at fetal death was developed and evaluated.

Methods

The algorithm developed by the Stillbirth Collaborative Research Network (SCRN) incorporated clinical and post‐mortem data. The SCRN conducted a population‐based case–control study of women with stillbirths and livebirths from 2006 to 2008 in five geographical catchment areas. Rules were developed to estimate a due date, identify an interval during which death likely occurred, and estimate GA at the time of fetal death. Reliability of using fetal foot length to estimate GA at death was assessed.

Results

The due date estimated for 620 singleton stillbirths studied was considered clinically reliable for 87%. Only 25.2% of stillbirths were documented alive within 2 days before diagnosis and 47.6% within 1 week of diagnosis. The algorithm‐derived estimate of GA at time of fetal death was one or more weeks earlier than the GA at delivery for 43.5% of stillbirths. GA estimated from fetal foot length agreed with GA by algorithm within 2 weeks for 75% within a subset of well‐dated stillbirths.

Conclusions

Precise assignment of GA at death, defined as reliable dating criteria and a short interval (≤1 week) during which fetal death was known to have occurred, was possible in 46.6% of cases. Fetal foot length is a relatively accurate measure of GA at death and should be collected in all stillbirth cases.
Differences in Birthweight Curves Between Newborns of Immigrant Mothers vs. Infants Born in Their Corresponding Native Countries: Systematic Overview
Authors: Boshari Talia , Urquia Marcelo L. , Sgro Michael , De Souza Leanne R. , Ray Joel G.
Published: October 2013

Background

Newborn weight may vary between ethnic groups, but it is not known if birthweight differences exist between term babies born to immigrant mothers compared with those born in their corresponding native countries.

Methods

We completed a systematic review of all birthweight curves published between 1980 and 2012, based on at least 100 singleton deliveries. We compared the 10th, 50th and 90th percentile birthweight values at 40 weeks gestation for male and female infants born in their native country vs. those infants born to mothers who had emigrated from their native country to Ontario, Canada. For the 50th percentile values, we also calculated a standardised pooled weighted difference and 95% confidence interval [CI] for both sexes. We also assessed whether birthweight differed over time, or if the differences varied by the Human Development Index (HDI) value for the native country.

Results

A total of 31 studies from 21 different countries met the inclusion criteria, comprising 13 317 578 males and 12 859 119 females born at 40 weeks gestation. There was a small non‐significant rise in reported birthweight percentile values between 1983 and 2006. Nearly all infants born to women in their native country had lower birthweights than those born to mothers who had emigrated from the same country to Canada at the 10th, 50th and 90th percentiles. Overall, the 50th percentile weights differed by 115 g [95% CI 74, 156] for males and 122 g [95% CI 95, 150] for females. As HDI or median birthweight increased, birthweight differences were less pronounced, but not significantly so.

Conclusions

Term birthweight percentiles are typically higher among term infants born to mother who immigrate to Canada than those of infants born in their respective native country.
A Test of Agreement of Customised Birthweight Models
Authors: Gibbons Kristen S. , Chang Allan M. Z. , Flenady Vicki J. , Mahomed Kassam , Gray Peter H. , Gardener Glenn J. , Rossouw Dominique
Published: October 2013

Background

The objective of this study was to determine whether the physiological effects on birthweight as described by customised birthweight models (CBMs) from various populations and locations are consistent when applied to a single sample.

Methods

The predicted birthweight was calculated for 52 826 White‐European singleton term births between 1997 and 2008 from a large Australian hospital using the same set of variables from 12 published CBMs. The accuracy of prediction was tested against both the actual birthweight and a reference model. Intraclass correlation coefficients (ICCs) along with 95% confidence intervals of the measurements, paired differences (predicted–actual birthweight) and absolute values of the paired differences are reported.

Results

The average difference in predicted and actual birthweight was <200 g for all CBMs, with ICCs for all but one model indicating fair agreement (between 0.3 and 0.5). When compared with the reference model, eight of the 11 models had a difference in predicted birthweight of <220 g, and the ICCs indicated that the majority of models had strong agreement.

Conclusion

All published CBMs demonstrated ability to predict birthweight with reasonable accuracy. The effects of maternal and fetal characteristics on birthweight appear to be consistent across birthweight models. This finding is a further step in validating the CBM, and provides greater evidence for the creation of a global model.
Small but thick enough – the Arabidopsis hypocotyl as a model to study secondary growth
Authors: Ragni Laura , Hardtke Christian S.
Published: October 2013

The continuous production of vascular tissues through secondary growth results in radial thickening of plant organs and is pivotal for various aspects of plant growth and physiology, such as water transport capacity or resistance to mechanical stress. It is driven by the vascular cambium, which produces inward secondary xylem and outward secondary phloem. In the herbaceous plant Arabidopsis thaliana (Arabidopsis), secondary growth occurs in stems, in roots and in the hypocotyl. In the latter, radial growth is most prominent and not obscured by parallel ongoing elongation growth. Moreover, its progression is reminiscent of the secondary growth mode of tree trunks. Thus, the Arabidopsis hypocotyl is a very good model to study basic molecular mechanisms of secondary growth. Genetic approaches have succeeded in the identification of various factors, including peptides, receptors, transcription factors and hormones, which appear to participate in a complex network that controls radial growth. Many of these players are conserved between herbaceous and woody plants. In this review, we will focus on what is known about molecular mechanisms and regulators of vascular secondary growth in the Arabidopsis hypocotyl.
Foreign Investment and Technological Spillovers in Kenya: Extent and Mode of Occurrence
Authors: Gachino Geoffrey G.
Published: October 2013

This paper uses a uniquely designed analytical framework based on technological learning and capability development to examine the extent of multinational company spillover occurrence in the Kenyan manufacturing industry. Using a firm‐level survey data, we examined the kind of spillovers occurring, extent of occurrence as well as the channels through which such spillovers occurred. The results obtained showed that the main kinds of spillovers occurring were product and process spillovers followed by marketing, management and organisation. Results of t‐tests analysis showed significant differences between competition and demonstration, and linkage and labour mobility implying that the first two mechanisms were extremely important in spillover occurrence compared with the latter two in the Kenyan context. These have implications that linkage and labour mobility have weaker learning effects, hence weak in stimulating capability building. T‐test analysis showed that more spillovers occurred from foreign firms than from locally owned firms. The results also showed that spillovers were likely to occur due to foreign presence, firm and machine age, skill level, research and development, training and participation in imports. Based on the results generated, the paper portends that foreign direct investment can play an important role in the country's manufacturing industry by stimulating learning and capability development via spillover occurrence.
Purifying the Ranks: Ethnic and Minority Policy in theRomanianArmedForces during theSecondWorldWar
Authors: Harward Grant
Published: October 2013

During theSecondWorld War, the Romanian Armed Forces joined in the conflict between NaziGermany and SovietRussia. The Romanian Army's contribution to the Axis war effort has been largely forgotten or sidelined since the war. Similarly,Romania's minorities and their military service or restriction from military service has been overlooked.Romania's expansion after the FirstWorld War greatly increased the number of minorities in the country and also those serving in the military. The way the Romanian Armed Forces dealt with minorities and their contribution to the Romanian war effort should not be forgotten as the true extent and depth of the war on the Eastern Front is being revealed. Romanian nationalist and ethnic policies affected the ranks as much as it shaped the rest of its wartime policy of ethnic ‘purification’.
Mother–infant Interaction Quality and Infants' Ability to Encode Actions as Goal‐directed
Authors: Licata Maria , Paulus Markus , Thoermer Claudia , Kristen Susanne , Woodward Amanda L. , Sodian Beate
Published: October 2013

The current study investigated the relationship between mother–child interaction quality and infants' ability to interpret actions as goal‐directed at 7 months in a sample of 37 dyads. Interaction quality was assessed in a free play interaction using two distinct methods: one assessed the overall affective quality (emotional availability), and one focused on the mother's proclivity to treat her infant as an intentional agent (mind‐mindedness). Furthermore, infants' ability to interpret human actions as goal‐directed was assessed. Analyses revealed that only maternal emotional availability, and not maternal mind‐mindedness, was related to infants' goal‐encoding ability. This link remained stable even when controlling for child temperament, working memory, and maternal education. These findings provide first evidence that emotionally available caregiving promotes social‐cognitive development in preverbal infants.
Reciprocal Peer Dislike and Psychosocial Adjustment in Childhood
Authors: Betts Lucy R. , Stiller James
Published: October 2013

Reciprocal peer dislike was examined as a predictor of school adjustment and social relationship quality. One hundred and fifty‐one [69 male and 74 female, mean (M)age = 9.53, standard deviation (SD)age = .63 years] children completed measures of school liking, loneliness, and friendship quality twice over three months. From ratings of the amount of time participants liked to spend with individual classmates, social network analyses were used to determine reciprocal peer dislike. Curvilinear regression analyses revealed that reciprocal peer dislike at Time 1 predicted changes in the children's loneliness and friendship quality assessed as help, security, and closeness over three months. The findings support the conclusion that reciprocal peer dislike predicts aspects of school adjustment and social relationship qualities.
HLA‐DRB1*03:49, a novel allele identified by group‐specific sequence‐based typing in a north European individual
Authors: Wallis‐Jones S. , McWhinnie A. J. , Madrigal J. A. , Latham K. , Marsh S. G. E.
Published: October 2013

Identification of the antigen presenting molecule HLA‐DRB1*03:49 by group‐specific sequence‐based typing.
Obesity, diabetes and pneumonia: the menacing interface of non‐communicable and infectious diseases
Authors: Fisher‐Hoch Susan P. , Mathews Christine E. , McCormick Joseph B.
Published: October 2013

Objectives

To review current knowledge on the epidemiological, clinical and biological impact of the pandemic of obesity and diabetes on pneumonias.

Methods

We conducted a literature review using PubMed and EMBASE, supplemented by various sources. Given the disparate and fragmented nature of the literature, a formal systematic review was not possible.

Results

In 2008, globally 10% of men and 14% of women were obese and an estimated 371 million had diabetes; half undiagnosed and many obese. Numbers are rising rapidly in low‐ and middle‐income countries where the majority reside, but reliable data are lacking. The most frequent pneumonias in obesity and diabetes are tuberculosis, influenza and pneumococcal, staphylococcal and opportunistic pathogens. Diabetes impacts tuberculosis control and increases drug resistance and mortality. Mortality and morbidity from pneumococcal pneumonia and influenza are increased in obesity and diabetes. In addition to mechanical and physiological effects, there are considerable immunological abnormalities characterised by chronic, low‐grade inflammation. Simultaneous up‐regulation and dysregulation of both innate and adaptive immune responses impair control and killing of invading organisms. Prevention in those at risk is poorly practised, although screening for tuberculosis in diabetes is beginning in high‐burden settings.

Conclusions

Pneumonia is a threat globally in obesity and diabetes with increased incidence and severity of disease. There is uncertainty about whether vaccines are equally effective in those with obesity and diabetes. Increased epidemiological, clinical and biological knowledge will be crucial to face this 21st century challenge.
Squamous vulval cancer–an update
Authors: Bailey Claire , Luesley David
Published: October 2013

Key content

Squamous vulval cancer is a rare condition with a poorly understood aetiology. Two factors seem to have an important role; infection with human papilloma virus leading to vulva intraepithelial neoplasia and chronic inflammatory vulval dermatoses such as lichen sclerosus.

Diagnosis based on biopsy and management is complex. Consideration is given to site and size of lesion as well as the FIGO staging system.

Depending on the stage of cancer, other treatment modalities such as chemoradiation may play a role in the management of the condition.

Learning objectives

To know how to perform an incisional biopsy of a suspicious vulval lesion.

To acknowledge that incisional biopsy is the preferred mode of diagnosis for vulval cancer and appreciate that the role of wide local excision is limited.

To be aware of the use of sentinel node biopsy in the management of vulval cancer.

To understand that reconstructive surgery has an important place in the management of these patients.

Ethical issue

How can health professionals help women cope with the psychosexual sequelae after vulval surgery?
A β–glucuronosyltransferase from Arabidopsis thaliana involved in biosynthesis of type II arabinogalactan has a role in cell elongation during seedling growth
Authors: Knoch Eva , Dilokpimol Adiphol , Tryfona Theodora , Poulsen Christian P. , Xiong Guangyan , Harholt Jesper , Petersen Bent L. , Ulvskov Peter , Hadi Masood Z. , Kotake Toshihisa , Tsumuraya Yoichi , Pauly Markus , Dupree Paul , Geshi Naomi
Published: October 2013

We have characterized a β–glucuronosyltransferase (AtGlcAT14A) from Arabidopsis thaliana that is involved in the biosynthesis of type II arabinogalactan (AG). This enzyme belongs to the Carbohydrate Active Enzyme database glycosyltransferase family 14 (GT14). The protein was localized to the Golgi apparatus when transiently expressed in Nicotiana benthamiana. The soluble catalytic domain expressed in Pichia pastoris transferred glucuronic acid (GlcA) to β–1,6–galactooligosaccharides with degrees of polymerization (DP) ranging from 3–11, and to β–1,3–galactooligosaccharides of DP5 and 7, indicating that the enzyme is a glucuronosyltransferase that modifies both the β–1,6‐ and β–1,3‐galactan present in type II AG. Two allelic T–DNA insertion mutant lines showed 20–35% enhanced cell elongation during seedling growth compared to wild‐type. Analyses of AG isolated from the mutants revealed a reduction of GlcA substitution on Gal–β–1,6–Gal and β–1,3–Gal, indicating an in vivo role of AtGlcAT14A in synthesis of those structures in type II AG. Moreover, a relative increase in the levels of 3‐, 6‐ and 3,6‐linked galactose (Gal) and reduced levels of 3‐, 2‐ and 2,5‐linked arabinose (Ara) were seen, suggesting that the mutation in AtGlcAT14A results in a relative increase of the longer and branched β–1,3‐ and β–1,6‐galactans. This increase of galactosylation in the mutants is most likely caused by increased availability of the O6 position of Gal, which is a shared acceptor site for AtGlcAT14A and galactosyltransferases in synthesis of type II AG, and thus addition of GlcA may terminate Gal chain extension. We discuss a role for the glucuronosyltransferase in the biosynthesis of type II AG, with a biological role during seedling growth.
Complementarity to an miRNA seed region is sufficient to induce moderate repression of a target transcript in the unicellular green alga Chlamydomonas reinhardtii
Authors: Yamasaki Tomohito , Voshall Adam , Kim Eun‐Jeong , Moriyama Etsuko , Cerutti Heriberto , Ohama Takeshi
Published: October 2013

MicroRNAs (miRNAs) are 20–24 nt non‐coding RNAs that play important regulatory roles in a broad range of eukaryotes by pairing with mRNAs to direct post‐transcriptional repression. The mechanistic details of miRNA‐mediated post‐transcriptional regulation have been well documented in multicellular model organisms. However, this process remains poorly studied in algae such as Chlamydomonas reinhardtii, and specific features of miRNA biogenesis, target mRNA recognition and subsequent silencing are not well understood. In this study, we report on the characterization of a Chlamydomonas miRNA, cre‐miR1174.2, , which is processed from a near‐perfect hairpin RNA. Using Gaussia luciferase (gluc) reporter genes, we have demonstrated that cre‐miR1174.2 is functional in Chlamydomonas and capable of triggering site‐specific cleavage at the center of a perfectly complementary target sequence. A mismatch tolerance test assay, based on pools of transgenic strains, revealed that target hybridization to nucleotides of the seed region, at the 5′ end of an miRNA, was sufficient to induce moderate repression of expression. In contrast, pairing to the 3′ region of the miRNA was not critical for silencing. Our results suggest that the base‐pairing requirements for small RNA‐mediated repression in C. reinhardtii are more similar to those of metazoans compared with the extensive complementarity that is typical of land plants. Individual Chlamydomonas miRNAs may potentially modulate the expression of numerous endogenous targets as a result of these relaxed base‐pairing requirements.
Next‐generation sequencing, FISH mapping and synteny‐based modeling reveal mechanisms of decreasing dysploidy in Cucumis
Authors: Yang Luming , Koo Dal‐Hoe , Li Dawei , Zhang Tao , Jiang Jiming , Luan Feishi , Renner Susanne S. , Hénaff Elizabeth , Sanseverino Walter , Garcia‐Mas Jordi , Casacuberta Josep , Senalik Douglas A. , Simon Philipp W. , Chen Jinfeng , Weng Yiqun
Published: October 2013

In the large Cucurbitaceae genus Cucumis, cucumber (C. sativus) is the only species with 2n = 2x = 14 chromosomes. The majority of the remaining species, including melon (C. melo) and the sister species of cucumber, C. hystrix, have 2n = 2x = 24 chromosomes, implying a reduction from n = 12 to n = 7. To understand the underlying mechanisms, we investigated chromosome synteny among cucumber, C. hystrix and melon using integrated and complementary approaches. We identified 14 inversions and a C. hystrix lineage‐specific reciprocal inversion between C. hystrix and melon. The results reveal the location and orientation of 53 C. hystrix syntenic blocks on the seven cucumber chromosomes, and allow us to infer at least 59 chromosome rearrangement events that led to the seven cucumber chromosomes, including five fusions, four translocations, and 50 inversions. The 12 inferred chromosomes (AK1–AK12) of an ancestor similar to melon and C. hystrix had strikingly different evolutionary fates, with cucumber chromosome C1 apparently resulting from insertion of chromosome AK12 into the centromeric region of translocated AK2/AK8, cucumber chromosome C3 originating from a Robertsonian‐like translocation between AK4 and AK6, and cucumber chromosome C5 originating from fusion of AK9 and AK10. Chromosomes C2, C4 and C6 were the result of complex reshuffling of syntenic blocks from three (AK3, AK5 and AK11), three (AK5, AK7 and AK8) and five (AK2, AK3, AK5, AK8 and AK11) ancestral chromosomes, respectively, through 33 fusion, translocation and inversion events. Previous results (Huang, S., Li, R., Zhang, Z. et al., , Nat. Genet. 41, 1275–1281; Li, D., Cuevas, H.E., Yang, L., Li, Y., Garcia‐Mas, J., Zalapa, J., Staub, J.E., Luan, F., Reddy, U., He, X., Gong, Z., Weng, Y. 2011a, BMC Genomics, 12, 396) showing that cucumber C7 stayed largely intact during the entire evolution of Cucumis are supported. Results from this study allow a fine‐scale understanding of the mechanisms of dysploid chromosome reduction that has not been achieved previously.
Prospective study of mobilization kinetics up to 18 hours after late‐afternoon dosing of plerixafor
Authors: Shi Patricia A. , Miller Lorraine K. , Isola Luis M.
Published: October 2013

Background

The current FDA‐approved time interval between plerixafor dosing and apheresis initiation is approximately 11 hours, but this time interval is impractical for most care providers. Few studies have examined mobilization kinetics beyond 11 hours in multiple myeloma (MM) and non‐Hodgkin's lymphoma (NHL) patients. Therefore, this study's intent was to analyze an interval of 17 to 18 hours between plerixafor dosing and apheresis initiation.

Study Design and Methods

In 11 patients with MM or NHL, 240 μg/kg plerixafor was administered at 5 p.m. on Day 4 of granulocyte–colony‐stimulating factor (G‐CSF) mobilization. Peripheral blood (PB) CD34+ and CD34+CD38− concentrations were enumerated every 2 hours until 7 a.m. and immediately before apheresis on Day 5, for a total interval time of 17 to 18 hours after plerixafor. Data were analyzed using mixed‐model analysis of repeated measures and paired t testing.

Results

Ten of the 11 subjects achieved a CD34+ product count of more than 2 × 106/kg with a single leukapheresis procedure. All 10 had a preplerixafor PB CD34+ concentration ([CD34+]) of at least 10/μL. PB [CD34+] was not different between 10 and 18 hours after plerixafor (p = 0.8). In contrast, PB CD34+CD38− concentrations significantly increased from 10 to 18 hours after plerixafor (p = 0.03).

Conclusions

In MM and NHL patients with adequate preplerixafor [CD34+], leukapheresis initiated 14 to 18 hours after plerixafor and G‐CSF mobilization may not impair adequate CD34+ collection and may increase more primitive CD34+CD38− collection. In this subset of patients, late‐afternoon dosing of plerixafor at 5 p.m. with initiation of next‐day apheresis as late as 11 a.m. appears feasible without loss of efficacy.
Human Exposure to Rabid Free‐Ranging Cats: A Continuing Public Health Concern in Pennsylvania
Authors: Campagnolo E. R. , Lind L. R. , Long J. M. , Moll M. E. , Rankin J. T. , Martin K. F. , Deasy M. P. , Dato V. M. , Ostroff S. M.
Published: October 2013

Rabid free‐ranging cats have been a public health concern in Pennsylvania since raccoon variant rabies first was recognized in the state in the early 1980s. Over the last decade, between 1.5 and 2.5% of cats submitted to Pennsylvania's state laboratories for rabies testing have been positive. In this report, we describe the extent of rabies in free‐ranging cats in Pennsylvania. We also present two examples of human exposure to rabid free‐ranging cats that occurred in Pennsylvania during 2010–2011 and the public health actions taken to address rabies exposure in the humans and animals. We then describe the concerns surrounding the unvaccinated and free‐ranging cat population in Pennsylvania and possible options in managing this public and animal health problem.
Diversity of vestibular nuclei neurons targeted by cerebellar nodulus inhibition
Authors: Meng Hui , Blázquez Pablo M. , Dickman J. David , Angelaki Dora E.
Published: October 2013

Key points

Electrical stimulation of the cerebellar nodulus and ventral uvula decreases the time constant of the horizontal vestibulo‐ocular reflex during yaw rotation.

Unlike the flocculus and ventral paraflocculus which target a particular cell group, nodulus/ventral uvula inhibition targets a large diversity of cell types in the vestibular nuclei.

Twenty per cent of nodulus/ventral uvula‐target neurons were sensitive to both vestibular stimuli and eye movements, whereas the majority was only sensitive to vestibular stimuli.

Most nodulus/ventral uvula‐target cells responded to both rotation and translation and only approximately half discriminated translational and gravitational accelerations.

Projections of the nodulus/ventral uvula to both eye movement‐and non‐eye movement‐sensitive vestibular nuclei neurons suggest a role in both eye movement generation and vestibulo‐spinal or thalamo‐cortical systems.

Abstract  A functional role of the cerebellar nodulus and ventral uvula (lobules X and IXc,d of the vermis) for vestibular processing has been strongly suggested by direct reciprocal connections with the vestibular nuclei, as well as direct vestibular afferent inputs as mossy fibres. Here we have explored the types of neurons in the macaque vestibular nuclei targeted by nodulus/ventral uvula inhibition using orthodromic identification from the caudal vermis. We found that all nodulus‐target neurons are tuned to vestibular stimuli, and most are insensitive to eye movements. Such non‐eye‐movement neurons are thought to project to vestibulo‐spinal and/or thalamo‐cortical pathways. Less than 20% of nodulus‐target neurons were sensitive to eye movements, suggesting that the caudal vermis can also directly influence vestibulo‐ocular pathways. In general, response properties of nodulus‐target neurons were diverse, spanning the whole continuum previously described in the vestibular nuclei. Most nodulus‐target cells responded to both rotation and translation stimuli and only a few were selectively tuned to translation motion only. Other neurons were sensitive to net linear acceleration, similar to otolith afferents. These results demonstrate that, unlike the flocculus and ventral paraflocculus which target a particular cell group, nodulus/ventral uvula inhibition targets a large diversity of cell types in the vestibular nuclei, consistent with a broad functional significance contributing to vestibulo‐ocular, vestibulo‐thalamic and vestibulo‐spinal pathways.
Adaptive Partial Differential Equation Observer for Battery State-of-Charge/State-of-Health Estimation Via an Electrochemical Model
Authors: Moura Scott J. , Chaturvedi Nalin A. , Krstić Miroslav
Published: October 2013

This paper develops an adaptive partial differential equation (PDE) observer for battery state-of-charge (SOC) and state-of-health (SOH) estimation. Real-time state and parameter information enables operation near physical limits without compromising durability, thereby unlocking the full potential of battery energy storage. SOC/SOH estimation is technically challenging because battery dynamics are governed by electrochemical principles, mathematically modeled by PDEs. We cast this problem as a simultaneous state (SOC) and parameter (SOH) estimation design for a linear PDE with a nonlinear output mapping. Several new theoretical ideas are developed, integrated together, and tested. These include a backstepping PDE state estimator, a Padé-based parameter identifier, nonlinear parameter sensitivity analysis, and adaptive inversion of nonlinear output functions. The key novelty of this design is a combined SOC/SOH battery estimation algorithm that identifies physical system variables, from measurements of voltage and current only.
Viral Defenses
Authors: Riddihough Guy
Published: October 2013

Certain mammalian cells can use RNAi in the innate defense against invading viruses.
Preclinical Characterization of GSK2336805, a Novel Inhibitor of Hepatitis C Virus Replication That Selects for Resistance in NS5A
Authors: Walker Jill , Crosby Renae , Wang Amy , Woldu Ermias , Vamathevan Jessica , Voitenleitner Christian , You Shihyun , Remlinger Katja , Duan Maoshang , Kazmierski Wieslaw , Hamatake Robert
Published: October 2013

GSK2336805 is an inhibitor of hepatitis C virus (HCV) with picomolar activity on the standard genotype 1a, 1b, and 2a subgenomic replicons and exhibits a modest serum shift. GSK2336805 was not active on 22 RNA and DNA viruses that were profiled. We have identified changes in the N-terminal region of NS5A that cause a decrease in the activity of GSK2336805. These mutations in the genotype 1b replicon showed modest shifts in compound activity (<13-fold), while mutations identified in the genotype 1a replicon had a more dramatic impact on potency. GSK2336805 retained activity on chimeric replicons containing NS5A patient sequences from genotype 1 and patient and consensus sequences for genotypes 4 and 5 and part of genotype 6. Combination and cross-resistance studies demonstrated that GSK2336805 could be used as a component of a multidrug HCV regimen either with the current standard of care or in combination with compounds with different mechanisms of action that are still progressing through clinical development.
Efflux Inhibition with Verapamil Potentiates Bedaquiline in Mycobacterium tuberculosis
Authors: Gupta Shashank , Cohen Keira A. , Winglee Kathryn , Maiga Mamoudou , Diarra Bassirou , Bishai William R.
Published: October 2013

Drug efflux is an important resistance mechanism in
Mycobacterium tuberculosis
. We found that verapamil, an efflux inhibitor, profoundly decreases the MIC of bedaquiline and clofazimine to
M. tuberculosis
by 8- to 16-fold. This exquisite susceptibility was noted among drug-susceptible and drug-resistant clinical isolates. Thus, efflux inhibition is an important sensitizer of bedaquiline and clofazimine, and efflux may emerge as a resistance mechanism to these drugs.
Can Levofloxacin Be a Useful Alternative to Trimethoprim-Sulfamethoxazole for Treating Stenotrophomonas maltophilia Bacteremia?
Authors: Cho Sun Young , Kang Cheol-In , Kim Jungok , Ha Young Eun , Chung Doo Ryeon , Lee Nam Yong , Peck Kyong Ran , Song Jae-Hoon
Published: October 2013

A retrospective study was conducted to evaluate the efficacy of levofloxacin in the treatment of
Stenotrophomonas maltophilia
bacteremia. The 30-day mortality rates were similar between the trimerthoprim-sulfamethoxazole (TMP-SMX) and levofloxacin treatment groups. Adverse events related to antibiotics occurred more frequently in patients receiving TMP-SMX, and recurrent bacteremia due to levofloxacin-resistant
S. maltophilia
strains developed in patients treated with levofloxacin. Our data suggest that levofloxacin can be a useful alternative option for treating
S. maltophilia
infections.
Differentiation of Antigen-Specific T Cells with Limited Functional Capacity during Mycobacterium tuberculosis Infection
Authors: Jeong Yun Hee , Jeon Bo-Young , Gu Sun-Hwa , Cho Sang-Nae , Shin Sung Jae , Chang Jun , Ha Sang-Jun
Published: October 2013

Despite the generation ofMycobacterium tuberculosis-specific T cell immune responses during the course of infection, only 5 to 10% of exposed individuals develop active disease, while others develop a latent infection. This phenomenon suggests defectiveM. tuberculosis-specific immunity, which necessitates more careful characterization ofM. tuberculosis-specific T cell responses. Here, we longitudinally analyzed the phenotypes and functions ofM. tuberculosis-specific T cells. In contrast to the functional exhaustion of T cells observed after chronic infection,M. tuberculosis-specific CD8+T cells differentiated into either effector (CD127loCD62Llo) or effector memory (CD127hiCD62Llo) cells, but not central memory cells (CD127hiCD62Lhi), with low programmed death 1 (PD-1) expression, even in the presence of high levels of bacteria. Additionally,M. tuberculosis-specific CD8+and CD4+T cells produced substantial levels of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), but not interleukin 2 (IL-2), uponin vitrorestimulation. AmongM. tuberculosis-specific CD8+T cells, CD127hieffector memory cells displayed slower ongoing turnover but greater survival potential. In addition, these cells produced more IFN-γ and TNF-α and displayed lytic activity upon antigen stimulation. However, the effector function ofM. tuberculosis-specific CD8+CD127hieffector memory T cells was inferior to that of canonical CD8+CD127himemory T cells generated after acute lymphocytic choriomeningitis virus infection. Collectively, our data demonstrate thatM. tuberculosis-specific T cells can differentiate into memory T cells during the course ofM. tuberculosisinfection independent of the bacterial burden but with limited functionality. These results provide a framework for further understanding the mechanisms ofM. tuberculosisinfection that can be used to develop more effective vaccines.