bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA transposition by protein transduction of the piggyBac transposase from lentiviral Gag precursors
Authors: Cai Yujia , Bak Rasmus O. , Krogh Louise Bechmann , Staunstrup Nicklas H. , Moldt Brian , Corydon Thomas J. , Schrøder Lisbeth Dahl , Mikkelsen Jacob Giehm
Published: November 2013

DNA transposon-based vectors have emerged as gene vehicles with a wide biomedical and therapeutic potential. So far, genomic insertion of such vectors has relied on the co-delivery of genetic material encoding the gene-inserting transposase protein, raising concerns related to persistent expression, insertional mutagenesis and cytotoxicity. This report describes potent DNA transposition achieved by direct delivery of transposase protein. By adapting integrase-deficient lentiviral particles (LPs) as carriers of the hyperactive piggyBac transposase protein (hyPBase), we demonstrate rates of DNA transposition that are comparable with the efficiency of a conventional plasmid-based strategy. Embedded in the Gag polypeptide, hyPBase is robustly incorporated into LPs and liberated from the viral proteins by the viral protease during particle maturation. We demonstrate lentiviral co-delivery of the transposase protein and vector RNA carrying the transposon sequence, allowing robust DNA transposition in a variety of cell types. Importantly, this novel delivery method facilitates a balanced cellular uptake of hyPBase, as shown by confocal microscopy, and allows high-efficiency production of clones harboring a single transposon insertion. Our findings establish engineered LPs as a new tool for transposase delivery. We believe that protein transduction methods will increase applicability and safety of DNA transposon-based vector technologies.
Mangrovibacterium diazotrophicum gen. nov., sp. nov., a nitrogen-fixing bacterium isolated from a mangrove sediment, and proposal of Prolixibacteraceae fam. nov.
Authors: Huang Xiao-Fang , Liu Yu Juan , Dong Jun-De , Qu Ling-Yun , Zhang Yan-Ying , Wang Fa-Zuo , Tian Xin-Peng , Zhang Si
Published: November 2013

A nitrogen-fixing bacterium, designated strain SCSIO N0430T, was isolated from a mangrove sediment sample. Analysis of the sequence of the nifH gene responsible for nitrogen fixation in this strain indicated a close relationship to an uncultured bacterium ZNZ-D11 (GenBank accession no. JF896696). 16S rRNA gene sequence analysis revealed that this isolate had less than 93 % similarity to its closest relative,

Sunxiuqinia elliptica

DQHS4T. A phylogenetic tree reconstructed based on 16S rRNA gene sequences revealed that strain SCSIO N0430T was a member of the phylum

Bacteroidetes

. Chemotaxonomic and physiological characteristics, including phospholipids and major fatty acids, readily distinguished the isolate from established members of the phylum

Bacteroidetes

. It is concluded that strain SCSIO N0430T represents a novel genus and species, for which the name Mangrovibacterium diazotrophicum gen. nov., sp. nov. is proposed, with the type strain of the species SCSIO N0430T ( = KCTC 32129T = DSM 27148T = JCM 19152T). Based on phylogenetic characteristics and 16S rRNA gene signature nucleotide patterns, the three genera

Sunxiuqinia

,

Prolixibacter

and Mangrovibacterium are proposed to make up a novel family, Prolixibacteraceae fam. nov., in the order

Bacteroidales

.
Phyllobacterium loti sp. nov. isolated from nodules of Lotus corniculatus
Authors: Sánchez Maximo , Ramírez-Bahena Martha-Helena , Peix Alvaro , Lorite María J. , Sanjuán Juan , Velázquez Encarna , Monza Jorge
Published: November 2013

Strain S658T was isolated from a Lotus corniculatus nodule in a soil sample obtained in Uruguay. Phylogenetic analysis of the 16S rRNA gene and atpD gene showed that this strain clustered within the genus

Phyllobacterium

. The closest related species was, in both cases,

Phyllobacterium trifolii

PETP02T with 99.8 % sequence similarity in the 16S rRNA gene and 96.1 % in the atpD gene. The 16S rRNA gene contains an insert at the beginning of the sequence that has no similarities with other inserts present in the same gene in described rhizobial species. Ubiquinone Q-10 was the only quinone detected. Strain S658T differed from its closest relatives through its growth in diverse culture conditions and in the assimilation of several carbon sources. It was not able to reproduce nodules in Lotus corniculatus. The results of DNA–DNA hybridization, phenotypic tests and fatty acid analyses confirmed that this strain should be classified as a representative of a novel species of the genus

Phyllobacterium

, for which the name Phyllobacterium loti sp. nov. is proposed. The type strain is S658T( = LMG 27289T = CECT 8230T).
Paenalcaligenes suwonensis sp. nov., isolated from spent mushroom compost
Authors: Moon Ji-Young , Lim Jun-Muk , Ahn Jae-Hyung , Weon Hang-Yeon , Kwon Soon-Wo , Kim Soo-Jin
Published: November 2013

A bacterial strain, ABC02-12T, was isolated from spent mushroom compost, a waste product of button mushroom cultivation. Cells of the strain were Gram-stain-negative, catalase- and oxidase-positive, non-spore-forming, aerobic flagellated rods. Optimum growth occurred at 28 °C and pH 7.0. 16S rRNA gene sequence analysis showed that strain ABC02-12T shared the highest sequence similarities with

Paenalcaligenes hominis

CCUG 53761AT (96.0 %),

Alcaligenes faecalis subsp. parafaecalis

GT (95.7 %),

Alcaligenes faecalis subsp. faecalis

IAM 12369T (95.4 %) and

Pusillimonas noertemannii

BN9T (95.3 %). According to the phylogenetic tree, strain ABC02-12T formed a robust cluster with

Paenalcaligenes hominis

CCUG 53761AT and

Paenalcaligenes hermetiae

KBL009T. The quinone system was ubiquinone Q-8 with minor amounts of Q-7. The major fatty acids (>5 % of total fatty acids) were C16 : 0, C16 : 1ω6c and/or C16 : 1ω7c (summed feature 3), C18 : 1ω7c and/or C18 : 1ω6c (summed feature 8), C17 : 0 cyclo, and iso-C16 : 1 I, C14 : 0 3-OH and/or an unknown fatty acid (summed feature 2). The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unknown aminolipid. Putrescine was the principal polyamine, with small amounts of 2-hydroxyputrescine and cadaverine. On the basis of the evidence presented in this study, strain ABC02-12T is a representative of a novel species within the genus

Paenalcaligenes

, for which the name
Paenalcaligenes

suwonensis sp. nov. is proposed. The type strain is ABC02-12T ( = KACC 16537T = NBRC 108927T).
Genetic mutations of avian leukosis virus subgroup J strains extended their host range
Authors: Shen Yanwei , Cai Liming , Wang Yanming , Wei Rongrong , He Menglian , Wang Shanhui , Wang Guihua , Cheng Ziqiang
Published: November 2013

The genetic diversity of avian leukosis virus subgroup J (ALV-J) is determined not only by the env gene, but also by its 3′ UTR and 3′ LTR. They all play important roles in extending the host range and tumour development. In the present study, one ALV-J strain (ZB110604-6) from Black-Bone Silky Fowl (BSF) and three ALV-J strains (ZB110604-3/4/5) from grey partridge (GP), which bore multiple tumours and breed in one house of Farm A, were demonstrated extending their host to GP, while two other ALV-J strains (LC110515-3/4) from BSF of Farm B could not infect the embryo fibroblast of GP. The BSF is a unique species of chicken in China, while the GP is a close relative of the pheasant that previously demonstrated resistance to ALV-J. Histopathology showed that various tumours were induced by ALV-J in the two species. Phylogenetic tree analysis showed that the isolates from Farms A and B, rather than species, belong to two different clusters of ALV-J. Genetic mutations analysis revealed that the isolates obtained from Farm A showed a higher frequency of mutation in the hypervariable region 2 domain than in other variable regions of the gp85 gene. From the nucleotide alignment of the 3′ UTR and 3′ LTR gene, and the spectrum of tumours observed in this study, we speculate that the deletions or mutations in the redundant transmembrane region, E element and U3 (CAAT boxes, CArG box and Y box) might associate with tumour formation and development. The extension of the host range of ALV-J to the GP suggested that housing different species together provides more opportunities for ALV-J to evolve rapidly.
MICROTUBULE-ASSOCIATED PROTEIN65 Is Essential for Maintenance of Phragmoplast Bipolarity and Formation of the Cell Plate inPhyscomitrella patens
Authors: Kosetsu Ken , de Keijzer Jeroen , Janson Marcel E. , Goshima Gohta
Published: November 2013

The phragmoplast, a plant-specific apparatus that mediates cytokinesis, mainly consists of microtubules (MTs) arranged in a bipolar fashion, such that their plus ends interdigitate at the equator. Membrane vesicles are thought to move along the MTs toward the equator and fuse to form the cell plate. Although several genes required for phragmoplast MT organization have been identified, the mechanisms that maintain the bipolarity of phragmoplasts remain poorly understood. Here, we show that engaging phragmoplast MTs in a bipolar fashion in protonemal cells of the moss Physcomitrella patens requires the conserved MT cross-linking protein MICROTUBULE-ASSOCIATED PROTEIN65 (MAP65). Simultaneous knockdown of the three MAP65s expressed in those cells severely compromised MT interdigitation at the phragmoplast equator after anaphase onset, resulting in the collapse of the phragmoplast in telophase. Cytokinetic vesicles initially localized to the anaphase midzone as normal but failed to further accumulate in the next several minutes, although the bipolarity of the MT array was preserved. Our data indicate that the presence of bipolar MT arrays is insufficient for vesicle accumulation at the equator and further suggest that MAP65-mediated MT interdigitation is a prerequisite for maintenance of bipolarity of the phragmoplast and accumulation and/or fusion of cell plate–destined vesicles at the equatorial plane.
Fatalism and short‐termism as cultural barriers to cardiac rehabilitation among underprivileged men
Authors: Savage Mathieu , Dumas Alex , Stuart Stephen A
Published: November 2013

Cardiovascular diseases are a leading cause of death and disability in Canada, and individuals of low socioeconomic status appear particularly vulnerable to such disorders. Although many health‐related institutions have promoted cardiovascular health and have created cardiac rehabilitation programmes, they have not attained their desired outcomes, especially amongst socioeconomically deprived men. Drawing on Pierre Bourdieu's sociocultural theory, this qualitative study aims to understand the social mechanisms underpinning the lifestyles and health practices of men who had suffered a cardiovascular incident requiring hospitalisation. In all, 20 interviews were conducted with francophone men aged 40 to 65 years living in the province of Québec, Canada. The analysis strongly suggests that the respondents' living conditions and disease were significant obstacles to their adoption of a healthy lifestyle. Their despair and pessimism, apparently originating in the harshness of their financial realities, physical limitations and social networks, led them to believe that they could do little to control their lives, thereby limiting the fulfillment of any long‐term ambitions. Therefore, the adoption of a habitus characterised by fatalistic and short‐term perceptions of health influenced their lifestyle choices, leading them to maintain lives that were in stark contrast with the recommendations made by health promotion experts.
A novel inhibitor of the insulin/IGF signaling pathway protects from age‐onset, neurodegeneration‐linked proteotoxicity
Authors: El‐Ami Tayir , Moll Lorna , Carvalhal Marques Filipa , Volovik Yuli , Reuveni Hadas , Cohen Ehud
Published: November 2013

Aging manipulation is an emerging strategy aimed to postpone the manifestation of late‐onset neurodegenerative disorders such as Alzheimer's (AD) and Huntington's diseases (HD) and to slow their progression once emerged. Reducing the activity of the insulin/IGF signaling cascade (IIS), a prominent aging‐regulating pathway, protects worms from proteotoxicity of various aggregative proteins, including the AD‐associated peptide, Aβ‐ and the HD‐linked peptide, polyQ40. Similarly, IGF1 signaling reduction protects mice from AD‐like disease. These discoveries suggest that IIS inhibitors can serve as new drugs for the treatment of neurodegenerative maladies including AD and HD. Here, we report that NT219, a novel IIS inhibitor, mediates a long‐lasting, highly efficient inhibition of this signaling cascade by a dual mechanism; it reduces the autophosphorylation of the IGF1 receptor and directs the insulin receptor substrates 1 and 2 (IRS 1/2) for degradation. NT219 treatment promotes stress resistance and protects nematodes from AD‐ and HD‐associated proteotoxicity without affecting lifespan. Our discoveries strengthen the theme that IIS inhibition has a therapeutic potential as a cure for neurodegenerative maladies and point at NT219 as a promising compound for the treatment of these disorders through a selective manipulation of aging.
Should brief interventions in primary care address alcohol problems more strongly?
Authors: McCambridge Jim , Rollnick Stephen
Published: November 2013

Background

Brief interventions have well‐established small effects on alcohol consumption among hazardous and harmful drinkers in primary care, and national large‐scale programmes are being implemented in many countries for public health reasons.

Methods

This paper examines data from reviews and draws upon older brief intervention studies and recent developments in the literature on motivational interviewing to consider the capacity of brief interventions to benefit those with problems, including those with severe problems.

Results

Effects on alcohol problems have been shown much less consistently, and evidence cannot be claimed to be strong for any outcomes other than reduced consumption. Combinations of advice and motivational interviewing are a promising target for evaluation in trials, and more detailed studies of the conduct of brief interventions are needed.

Conclusions

We propose that brief interventions in primary care may be more effective if they offer appropriate content in a person‐centred manner, addressing patient concerns more directly.
Systematic review with meta‐analysis: clinical manifestations and management of autoimmune hepatitis in the elderly
Authors: Chen J. , Eslick G. D. , Weltman M.
Published: November 2013

Background

Autoimmune hepatitis is an uncommon chronic progressive inflammatory disease of the liver, characterised by hypergammaglobulianemia, circulating autoantibodies, and interface hepatitis histologically. It is traditionally thought to be a disease of young women. However, recent epidemiological and retrospective studies suggest that it might be a disease predominantly of older women. Studies of AIH in elderly patients have been fairly limited.

Aim

To investigate the differences in the clinical presentations and the management of AIH in the elderly and the younger patients.

Methods

We conducted a search on MEDLINE (from 1946), PubMed (1946) and EMBASE (1949) through to November 2013 using the terms ‘autoimmune hepatitis in the elderly’, and the combinations of ‘Autoimmune hepatitis’ AND the following terms: ‘elderly’, ‘aging’, ‘older patients’, and ‘older’. The reference lists of relevant articles were also searched for appropriate studies.

Results

A total of 1063 patients were identified with AIH in 10 retrospective studies. The definition of ‘elderly’ ranged from 60 to 65 years; 264 elderly and 592 younger patients were included for analysis. Elderly, 24.8%, were more likely to present asymptomatically, cirrhotic at presentation and HLA‐DR4‐positive. They are less likely to be HLA‐DR3‐positive and to relapse after treatment withdrawal after complete remission.

Conclusions

AIH is an important differential in elderly patients with cirrhosis or abnormal LFTs. Elderly are more likely to be cirrhotic and asymptomatic at presentation. Glucocorticoids use should be readily considered in the elderly patients as the current evidence suggests that they respond well to the therapy, with less relapse after treatment withdrawal.
The ultrastructural characters of the mature spermatozoon of Opechona bacillaris (Molin, 1859) (Digenea, Lepocreadiidae) a parasite of Scomber colias Gmelin, 1789 (Scombridae) off the coast of Dakar (Senegal)
Authors: Ndiaye Papa I. , Bakhoum Abdoulaye J. S. , Sène Aminata , Diagne Papa M. , Miquel Jordi
Published: November 2013

This study presents the ultrastructure of the mature spermatozoon of Opechona bacillaris, a digenean belonging to the family Lepocreadiidae. The sperm cell of O. bacillaris exhibits the general pattern described in most of the Lepocreadioidea: two axonemes of the 9 + ‘1’ pattern of the Trepaxonemata, mitochondria, a cortical mitochondrion, a nucleus, electron‐dense material in the anterior extremity of the spermatozoon, external ornamentation of the plasma membrane with associated spinelike bodies, and granules of glycogen. However, particularities of O. bacillaris are the simultaneous presence in the anterior extremity of the spermatozoon of the electron‐dense material, a mitochondrion, and the absence of cortical microtubules. In the Lepocreadiidae, we describe for the first time in O. bacillaris spinelike bodies associated with the external ornamentation of the plasma membrane and two mitochondria. The first mitochondrion is moniliform and composed of a mitochondrial cord with joined mitochondrial bulges. The second mitochondrion shows a regular form. The posterior tip of the spermatozoon has only singlets to owing to the disorganization of the second axoneme and granules of glycogen as occurs in Hypocreadium caputvadum, the other studied species of the family Lepocreadiidae.
Cold comfort at the Magh Mela: Social identity processes and physical hardship
Authors: Pandey Kavita , Stevenson Clifford , Shankar Shail , Hopkins Nicholas P. , Reicher Stephen D.
Published: November 2013

Humans inhabit environments that are both social and physical, and in this article we investigate if and how social identity processes shape the experience and negotiation of physically demanding environmental conditions. Specifically, we consider how severe cold can be interpreted and experienced in relation to group members' social identity. Our data comprise ethnographic observation and semi‐structured interviews with pilgrims attending a month‐long winter Hindu religious festival that is characterized by near‐freezing conditions. The analysis explores (1) how pilgrims appraised the cold and how these appraisals were shaped by their identity as pilgrims; (2) how shared identity with other pilgrims led to forms of mutual support that made it easier to cope with the cold. Our findings therefore extend theorizing on social identity processes to highlight their relevance to physical as well as social conditions.
Focusing on the bright tomorrow? A longitudinal study of organizational identification and projected continuity in a corporate merger
Authors: Lupina‐Wegener Anna , Drzensky Frank , Ullrich Johannes , van Dick Rolf
Published: November 2013

Past research provides evidence that organizational identification is a key factor predicting employees' behaviours during mergers and acquisitions. In particular, recent studies demonstrate that members of the subordinate merger partner, in contrast to the dominant group, often find it difficult to transfer their identification to the post‐merger organization. To understand this difference between dominant and subordinate groups, we examined employees' sense of projected continuity in the future. We argue that projected continuity mediates the differential relationships between pre‐merger and post‐merger identification and propose that pre‐merger identification relates positively to projected continuity in the dominant group but negatively in the subordinate group. As a result, the overall relationship between pre‐ and post‐merger identification should be reduced or eliminated in the subordinate compared with the dominant group. We tested our hypotheses in a survey (N = 492) distributed in a merger of two international pharmaceutical companies at the beginning of the post‐merger integration and 15 months later. Results were consistent with our assumptions of a moderated mediation effect. We conclude that a key challenge in merger integration is to support high identifiers in the subordinate group in developing a projected continuity or a focus on ‘the bright tomorrow’.
Determining the cost of obesity and its common comorbidities from a commercial claims database
Authors: Padula W. V. , Allen R. R. , Nair K. V.
Published: November 2013

What is already known about this subject

Obesity is highly prevalent and costly in the US.

Obesity often leads to other comorbid conditions, including diabetes and hypertension.

Obesity prevention efforts can reduce healthcare costs.

What this study adds

Obesity combined with other comorbidities significantly increases healthcare costs per patient visit.

The combination of obesity and depression exacerbates costs.

The most expensive series of chronic conditions in this study included obesity, diabetes, hypertension and depression.

Our objectives were to determine payments made by commercial healthcare providers in the US for adults diagnosed with obesity, and those comorbid with any combination of selected chronic conditions. Using a commercial claims and encounters database (n = 3 562 717), we evaluated an adult study population that had at least one in‐patient visit, outpatient visit or emergency department visit, and received a primary or secondary diagnosis of obesity. Persons were categorized by one or more comorbid diagnoses for diabetes mellitus, hypertension, depression or congestive heart failure. We adjusted for age and gender, and calculated the mean total net expenditures (in 2012, $US) for each combination of comorbid conditions based on individual visits to an in‐patient, outpatient or emergency department setting. Among 50 717 claims with diagnosis of obesity, the mean net expenditure for in‐patient and outpatient services was $ 1907 per patient per visit. Persons diagnosed with obesity and other comorbidities observed an increase in total net expenditures. Obesity and congestive heart failure observed the highest increase among single comorbidities at $ 5275. For persons with obesity and two other comorbidities, diabetes mellitus and depression was the highest at $ 15 226. The most expensive condition was obesity, diabetes mellitus, hypertension and depression at $ 15 733. Compared with average medical claims, persons diagnosed with obesity and other common chronic conditions experience significant increases in medical costs. These costs are often driven higher by time spent as in‐patients. By controlling and reducing the prevalence of obesity, we may see significant decreases in medical expenditures.
Two‐stage fatigue life evaluation of an aircraft fuselage panel with a bulging circumferential crack and a broken stringer
Authors: Sayar B. , Kayran A.
Published: November 2013

The article presents two‐stage fatigue life evaluation of a stiffened aluminium aircraft fuselage panel, subject to ground–air–ground pressure cycles, with a bulging circumferential crack and a broken stringer. As a worst‐case scenario, it is assumed that double cracks start at the edge of a rivet hole both in the skin and in the stringer simultaneously. In the first stage, fatigue crack growth analysis is performed until the stringer is completely broken with the crack on the fuselage skin propagating. After the stringer is completely broken, the effect of bulging crack on the fatigue life of the panel is investigated utilizing the stress intensity factors determined by the three‐dimensional finite element analyses of the fuselage panel with the broken stringer. It is concluded that bulging of the skin due to the internal pressure can have significant effect on the stress intensity factor, resulting in fast crack propagation after the stringer is completely broken.
Comparative field study evaluating the activity of recombinant factor VIII Fc fusion protein in plasma samples at clinical haemostasis laboratories
Authors: Sommer J. M. , Moore N. , McGuffie‐Valentine B. , Bardan S. , Buyue Y. , Kamphaus G. D. , Konkle B. A. , Pierce G. F.
Published: November 2013

Discrepancies exist for some of the modified coagulation factors when assayed with different one‐stage clotting and chromogenic substrate assay reagents. The aim of this study was to evaluate the performance of a recombinant factor VIII Fc fusion protein (rFVIIIFc), currently in clinical development for the treatment of severe haemophilia A, in a variety of one‐stage clotting and chromogenic substrate assays in clinical haemostasis laboratories. Haemophilic plasma samples spiked with rFVIIIFc or Advate® at 0.05, 0.20 or 0.80 IU mL−1 were tested by 30 laboratories using their routine procedures and plasma standards. Data were evaluated for intra‐ and inter‐laboratory variation, accuracy and possible rFVIIIFc‐specific assay discrepancies. For the one‐stage assay, mean recovery was 95% to 100% of expected for both Advate® and rFVIIIFc at 0.8 IU mL−1. Intra‐laboratory percent coefficient of variance (CV) ranged from 6.3% to 7.8% for Advate®, and 6.0% to 10.3% for rFVIIIFc. Inter‐laboratory CV ranged from 10% for Advate® and 16% for rFVIIIFc at 0.8 IU mL−1, to over 30% at 0.05 IU mL−1 for both products. For the chromogenic substrate assay, the average FVIII recovery was 107% ± 5% and 124% ± 8% of label potency across the three concentrations of Advate® and rFVIIIFc, respectively. Plasma rFVIIIFc levels can be monitored by either the one‐stage or the chromogenic substrate assay routinely performed in clinical laboratories without the need for a product‐specific rFVIIIFc laboratory standard. Accuracy by the one‐stage assay was comparable to that of Advate®, while marginally higher results may be observed for rFVIIIFc when using the chromogenic assay.
A study of prospective surveillance for inhibitors among persons with haemophilia in the United States
Authors: Soucie J. M. , Miller C. H. , Kelly F. M. , Payne A. B. , Creary M. , Bockenstedt P. L. , Kempton C. L. , Manco‐Johnson M. J. , Neff A. T. ,   the Haemophilia Inhibitor Research Study Investigators
Published: November 2013

Inhibitors are a rare but serious complication of treatment of patients with haemophilia. Phase III clinical trials enrol too few patients to adequately assess new product inhibitor risk. This project explores the feasibility of using a public health surveillance system to conduct national surveillance for inhibitors. Staff at 17 U.S. haemophilia treatment centres (HTC) enrolled patients with haemophilia A and B into this prospective study. HTC staff provided detailed historic data on product use and inhibitors at baseline, and postenrolment patients provided monthly detailed infusion logs. A central laboratory performed inhibitor tests on blood specimens that were collected at baseline, annually, prior to any planned product switch or when clinically indicated. The central laboratory also performed genotyping of all enrolled patients. From January 2006 through June 2012, 1163 patients were enrolled and followed up for 3329 person‐years. A total of 3048 inhibitor tests were performed and 23 new factor VIII inhibitors were identified, 61% of which were not clinically apparent. Infusion logs were submitted for 113 205 exposure days. Genotyping revealed 431 distinct mutations causing haemophilia, 151 of which had not previously been reported elsewhere in the world. This study provided critical information about the practical issues that must be addressed to successfully implement national inhibitor surveillance. Centralized testing with routine monitoring and confirmation of locally identified inhibitors will provide valid and representative data with which to evaluate inhibitor incidence and prevalence, monitor trends in occurrence rates and identify potential inhibitor outbreaks associated with products.
Species–area relationships across four trophic levels – decreasing island size truncates food chains
Authors: Roslin Tomas , Várkonyi Gergely , Koponen Martti , Vikberg Veli , Nieminen Marko
Published: November 2013

That larger areas will typically host more diverse ecological assemblages than small ones has been regarded as one of the few fundamental ‘laws’ in ecology. Yet, area may affect not only species diversity, but also the trophic structure of the local ecological assemblage. In this context, recent theory on trophic island biogeography offers two clear‐cut predictions: that the slope of the species–area relationship should increase with trophic rank, and that food chain length (i.e. the number of trophic levels) should increase with area. These predictions have rarely been verified in terrestrial systems. To offer a stringent test of key theory, we focused on local food chains consisting of trophic specialists: plants, lepidopteran herbivores, and their primary and secondary parasitoids. For each of these four trophic levels, we surveyed species richness across a set of 20 off‐shore continental islands spanning a hundred‐fold range in size. We then tested three specific hypotheses: that species richness is affected by island size, that the slope of the species–area curve is related to trophic rank, and that such differences in slope translate into variation in food chain length with island size. Consistent with these predictions, estimates of the species–area slope steepened from plants through herbivores and primary parasitoids to secondary parasitoids. As a result of the elevated sensitivity of top consumers to island size, food chain length decreased from large to small islands. Since island size did not detectably affect the ratio between generalists and specialists among either herbivores (polyphages vs oligophages) or parasitoids (idiobionts vs koinobionts), the patterns observed seemed more reflective of changes in the overall number of nodes and levels in local food webs than of changes in their linking structure. Overall, our results support the trophic‐level hypothesis of island biogeography. Per extension, they suggest that landscape modification may imperil food web integrity and vital biotic interactions.
Blaming the Kids: Children's Agency and Diminished Responsibility
Authors: Tiboris Michael
Published: November 2013

Children are less blameworthy for their beliefs and actions because they are young. But the relationship between development and responsibility is complex. What exactly grounds the excuses we rightly give to young agents? This article presents three distinct arguments for children's diminished responsibility. Drawing on significant resources from developmental psychology, it rejects views which base the normative adult/child distinction on children's inability to participate in certain kinds of moral communication or to form principled self‐conceptions which guide their actions. The article then argues that children's responsibility ought to be diminished because (and to the degree that) they are less competent at using features of their moral agency to meet social demands. This ‘normative competence’ view is philosophically defensible, supported by research in developmental psychology, and provides us with a method to evaluate whether things like peer pressure are relevant to responsibility.
Is Humility a Virtue in the Context of Sport?
Authors: Austin Michael W.
Published: November 2013

I define humility as a virtue that includes both proper self‐assessment and a self‐lowering other‐centeredness. I then argue that humility, so understood, is a virtue in the context of sport, for several reasons. Humility is a component of sportspersonship, deters egoism in sport, fuels athletic aspiration and risk‐taking, fosters athletic forms of self‐knowledge, decreases the likelihood of an athlete seeking to strongly humiliate her opponents or be weakly humiliated by them, and can motivate an athlete to achieve greater levels of excellence in her sport. In the context of team sports, humility can contribute to an athlete being a better teammate, foster unity amidst diversity within a team, and contribute to the overall moral and athletic excellence of a team. I also argue that an individual who is truly the world's greatest athlete can know and communicate this truth, while remaining humble.
Acute Phase Peyronie's Disease Management with Traction Device: A Nonrandomized Prospective Controlled Trial with Ultrasound Correlation
Authors: Martínez-Salamanca Juan I. , Egui Alejandra , Moncada Ignacio , Minaya Javier , Ballesteros Claudio Martínez , del Portillo Luis , Sola Ignacio , Carballido Joaquín
Published: November 2013

Introduction

Outcome data of penile traction therapy (PTT) for the acute phase (AP) of Peyronie's disease (PD) have not been specifically studied.

Aim

The aim of this study was to assess the effectiveness of a penile extender device for the treatment of patients with AP of PD.

Methods

A total of 55 patients underwent PTT for 6 months and were compared with 41 patients with AP of PD who did not receive active treatment (“no intervention group” [NIG]).

Main Outcomes Measures

Pre- and posttreatment variables included degree of curvature, penile length and girth, pain by 0–10 cm visual analog scale (VAS), erectile function (EF) domain of the International Index of Erectile Function questionnaire, Erection Hardness Scale, Sexual Encounter Profile 2 question, and penile sonographic evaluation (only patients in the intervention group).

Results

The mean curvature decreased from 33° at baseline to 15° at 6 months and 13° at 9 months with a mean decrease 20° (P < 0.05) in the PTT group. VAS score for pain decreased from 5.5 to 2.5 after 6 months (P < 0.05). EF and erection hardness also improved significantly. The percentage of patients who were not able to achieve penetration decreased from 62% to 20% (P < 0.03). In the NIG, deformity increased significantly, stretched flaccid penile length decreased, VAS score for pain increased, and EF and erection hardness worsened. PTT was associated with the disappearance of sonographic plaques in 48% of patients. Furthermore, the need for surgery was reduced in 40% of patients who would otherwise have been candidates for surgery and simplified the complexity of the surgical procedure (from grafting to plication) in one out of every three patients.

Conclusions

PTT seems an effective treatment for the AP of PD in terms of pain reduction, penile curvature decrease, and improvement in sexual function.
Ghrelin increases vagally mediated gastric activity by central sites of action
Authors: Swartz E. M. , Browning K. N. , A. Travagli R. , Holmes G. M.
Published: November 2013

Background

Vagally dependent gastric reflexes are mediated through vagal afferent fibers synapsing upon neurons of the nucleus tractus solitarius (NTS) which, in turn modulate the preganglionic parasympathetic dorsal motor nucleus of the vagus (DMV) neurons within the medullary dorsal vagal complex (DVC). The expression and transport of ghrelin receptors has been documented for the afferent vagus nerve, and functional studies have confirmed that vagal pathways are integral to ghrelin‐induced stimulation of gastric motility. However, the central actions of ghrelin within the DVC have not been explored fully.

Methods

We assessed the responses to ghrelin in fasted rats using: (i) in vivo measurements of gastric tone and motility following IVth ventricle application or unilateral microinjection of ghrelin into the DVC and (ii) whole cell recordings from gastric‐projecting neurons of the DMV.

Key Results

(i) IVth ventricle application or unilateral microinjection of ghrelin into the DVC‐elicited contractions of the gastric corpus via excitation of a vagal cholinergic efferent pathway and (ii) ghrelin facilitates excitatory, but not inhibitory, presynaptic transmission to DMV neurons.

Conclusions & Inferences

Our data indicate that ghrelin acts centrally by activating excitatory synaptic inputs onto DMV neurons, resulting in increased cholinergic drive by way of vagal motor innervation to the stomach.
Precise excision of plastid DNA by the large serine recombinase Bxb1
Authors: Shao Min , Kumar Shashi , Thomson James G.
Published: November 2013

Marker genes are essential for the selection and identification of rarely occurring transformation events generated in biotechnology. This includes plastid transformation, which requires that multiple copies of the modified chloroplast genome be present to obtain genetically stable transplastomic plants. However, the marker gene becomes dispensable when homoplastomic plants are obtained. Here, we demonstrate the precise excision of attP‐ and attB‐flanked DNA from the plastid genome mediated by the large serine recombinase Bxb1. We transformed the tobacco plastid genome with the pTCH‐PB vector containing a stuffer fragment of DNA flanked by directly oriented nonhomologous attP and attB recombinase recognition sites. In the absence of the Bxb1 recombinase, the transformed plastid genomes were stable and heritable. Nuclear‐transformed transgenic tobacco plants expressing a plastid‐targeted Bxb1 recombinase were crossed with transplastomic pTCH‐PB plants, and the T1 hybrids exhibited efficient excision of the target sequence. The Bxb1–att system should prove to be a useful tool for site‐specifically manipulating the plastid genome and generating marker‐free transplastomic plants.
Skeletal myopathy in heart failure: effects of aerobic exercise training
Authors: Brum P. C. , Bacurau A. V. , Cunha T. F. , Bechara L. R. G. , Moreira J. B. N.
Published: November 2013

New Findings

What is the topic of this review?

This symposium report addresses the effects of aerobic exercise training on skeletal muscle myopathy induced by heart failure (HF), with emphasis on the mechanisms involved in muscle atrophy.

What advances does it highlight?

It highlights the therapeutic effect of aerobic exercise training to combat skeletal myopathy in HF. Our results demonstrated that aerobic exercise training re‐established normal redox balance and prevented increased protein degradation by the ubiquitin–proteasome system, thereby preserving skeletal muscle mass in experimental models of HF. Our findings contribute to a better understanding of the mechanisms involved in skeletal myopathy in HF and the effects of training.

Reduced aerobic capacity, as measured by maximal oxygen uptake, is a hallmark in cardiovascular diseases and strongly predicts poor prognosis and higher mortality rates in heart failure patients. While exercise capacity is poorly correlated with cardiac function in this population, skeletal muscle abnormalities present a striking association with maximal oxygen uptake. This fact draws substantial attention to the clinical relevance of targeting skeletal myopathy in heart failure. Considering that skeletal muscle is highly responsive to aerobic exercise training, we addressed the benefits of aerobic exercise training to combat skeletal myopathy in heart failure, focusing on the mechanisms by which aerobic exercise training counteracts skeletal muscle atrophy.
Inactivation of Escherichia coli by Polychromatic Simulated Sunlight: Evidence for and Implications of a Fenton Mechanism Involving Iron, Hydrogen Peroxide, and Superoxide
Authors: Fisher Michael B. , Nelson Kara L.
Published: November 2013

Sunlight inactivation of
Escherichia coli
has previously been shown to accelerate in the presence of oxygen, exogenously added hydrogen peroxide, and bioavailable forms of exogenously added iron. In this study, mutants unable to effectively scavenge hydrogen peroxide or superoxide were found to be more sensitive to polychromatic simulated sunlight (without UVB wavelengths) than wild-type cells, while wild-type cells grown under low-iron conditions were less sensitive than cells grown in the presence of abundant iron. Furthermore, prior exposure to simulated sunlight was found to sensitize cells to subsequent hydrogen peroxide exposure in the dark, but this effect was attenuated for cells grown with low iron. Mutants deficient in recombination DNA repair were sensitized to simulated sunlight (without UVB wavelengths), but growth in the presence of iron chelators reduced the degree of sensitization conferred by this mutation. These findings support the hypothesis that hydrogen peroxide, superoxide, and intracellular iron all participate in the photoinactivation of
E. coli
and further suggest that the inactivation rate of enteric bacteria in the environment may be strongly dependent on iron availability and growth conditions.
Development of a Novel Selective and Differential Medium for the Isolation of Listeria monocytogenes
Authors: Park Sang-Hyun , Chang Pahn-Shick , Ryu Sangryeol , Kang Dong-Hyun
Published: November 2013

A new medium (lecithin and levofloxacin [LL] medium) is described for the isolation of
Listeria monocytogenes
from food samples. LL medium includes lecithin from soybeans for the detection of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific phospholipase C (PC-PLC) produced by
L. monocytogenes
. Levofloxacin is incorporated to inhibit the growth of microorganisms other than
L. monocytogenes
, especially
Bacillus cereus
, shown to possess PI-PLC and PC-PLC activities.
L. monocyogenes
produced white colonies with a halo on LL medium, whereas
Listeria innocua
appeared as white colonies without a halo. Levofloxacin at 0.20 mg/liter completely inhibited the growth of
B. cereus
, while the growth of
L. monocytogenes
was unaffected. In the second phase of the study, the sensitivity and the specificity of LL medium were compared to those of modified Oxford agar (MOX) and two chromogenic media (Brilliance
Listeria
agar and CHROMagar
Listeria
), using a total of 250 food samples. From 200 unspiked food samples, the specificity of LL medium (96.0%) was superior to that of MOX (72.0%) and similar to the specificities of Brilliance
Listeria
agar (96.5%) and CHROMagar
Listeria
(94.5%). From 50 spiked food samples, LL medium and CHROMagar
Listeria
represented the highest sensitivities (96.0%), followed by Brilliance
Listeria
agar (92.0%) and MOX (54.0%). Also, LL medium showed the highest confirmation rate (98.8%), followed by Brilliance
Listeria
agar (98.7%), CHROMagar
Listeria
(98.3%), and MOX (52.0%). On the basis of its good specificity and cost effectiveness, LL medium is useful for the isolation of
L. monocytogenes
from food samples.
Response of Xylella fastidiosa to Zinc: Decreased Culturability, Increased Exopolysaccharide Production, and Formation of Resilient Biofilms under Flow Conditions
Authors: Navarrete Fernando , De La Fuente Leonardo
Published: November 2013

The bacterial plant pathogen
Xylella fastidiosa
produces biofilm that accumulates in the host xylem vessels, affecting disease development in various crops and bacterial acquisition by insect vectors. Biofilms are sensitive to the chemical composition of the environment, and mineral elements being transported in the xylem are of special interest for this pathosystem. Here,
X. fastidiosa
liquid cultures were supplemented with zinc and compared with nonamended cultures to determine the effects of Zn on growth, biofilm, and exopolysaccharide (EPS) production under batch and flow culture conditions. The results show that Zn reduces growth and biofilm production under both conditions. However, in microfluidic chambers under liquid flow and with constant bacterial supplementation (closer to conditions inside the host), a dramatic increase in biofilm aggregates was seen in the Zn-amended medium. Biofilms formed under these conditions were strongly attached to surfaces and were not removed by medium flow. This phenomenon was correlated with increased EPS production in stationary-phase cells grown under high Zn concentrations. Zn did not cause greater adhesion to surfaces by individual cells. Additionally, viability analyses suggest that
X. fastidiosa
may be able to enter the viable but nonculturable state
in vitro
, and Zn can hasten the onset of this state. Together, these findings suggest that Zn can act as a stress factor with pleiotropic effects on
X. fastidiosa
and indicate that, although Zn could be used as a bactericide treatment, it could trigger the undesired effect of stronger biofilm formation upon reinoculation events.
Investigation of the
malE
Promoter and MalR, a Positive Regulator of the Maltose Regulon, for an Improved Expression System in Sulfolobus acidocaldarius
Authors: Wagner Michaela , Wagner Alexander , Ma Xiaoqing , Kort Julia Christin , Ghosh Abhrajyoti , Rauch Bernadette , Siebers Bettina , Albers Sonja-Verena
Published: November 2013

In this study, the regulator MalR (Saci_1161) of the TrmB family from
Sulfolobus acidocaldarius
was identified and was shown to be involved in transcriptional control of the maltose regulon (Saci_1660 to Saci_1666), including the ABC transporter (
malEFGK
), α-amylase (
amyA
), and α-glycosidase (
malA
). The Δ
malR
deletion mutant exhibited a significantly decreased growth rate on maltose and dextrin but not on sucrose. The expression of the genes organized in the maltose regulon was induced only in the presence of MalR and maltose in the growth medium, indicating that MalR, in contrast to its TrmB and TrmB-like homologues, is an activator of the maltose gene cluster. Electrophoretic mobility shift assays revealed that the binding of MalR to
malE
was independent of sugars. Here we report the identification of the archaeal maltose regulator protein MalR, which acts as an activator and controls the expression of genes involved in maltose transport and metabolic conversion in
S. acidocaldarius
, and its use for improvement of the
S. acidocaldarius
expression system under the control of an optimized maltose binding protein (
malE
) promoter by promoter mutagenesis.
Anti-Inflammatory Properties of Streptococcus salivarius, a Commensal Bacterium of the Oral Cavity and Digestive Tract
Authors: Kaci Ghalia , Goudercourt Denise , Dennin Véronique , Pot Bruno , Doré Joël , Ehrlich S. Dusko , Renault Pierre , Blottière Hervé M. , Daniel Catherine , Delorme Christine
Published: November 2013

Streptococcus salivarius
is one of the first colonizers of the human oral cavity and gut after birth and therefore may contribute to the establishment of immune homeostasis and regulation of host inflammatory responses. The anti-inflammatory potential of
S. salivarius
was first evaluated
in vitro
on human intestinal epithelial cells and human peripheral blood mononuclear cells. We show that live
S. salivarius
strains inhibited
in vitro
the activation of the NF-κB pathway on intestinal epithelial cells. We also demonstrate that the live
S. salivarius
JIM8772 strain significantly inhibited inflammation in severe and moderate colitis mouse models. These
in vitro
and
in vivo
anti-inflammatory properties were not found with heat-killed
S. salivarius
, suggesting a protective response exclusively with metabolically active bacteria.