bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeography of two freshwater prawn species from far-northern Queensland
Authors: Bernays Sofie J. , Schmidt Daniel J. , Hurwood David A. , Hughes Jane M.
Published: November 2014

The distribution of a freshwater species is often dependent on its ability to disperse within the riverine system. Species with high dispersal abilities tend to be widespread, whereas those with restricted dispersal tend to be geographically restricted and are usually given higher conservation priority. Population structure was compared between a widespread freshwater prawn species, Macrobrachium australiense, and a narrow-range endemic freshwater prawn, Macrobrachium koombooloomba. The distribution of M. australiense and M. koombooloomba did not overlap, although suggested historical river-boundary rearrangements indicate that there has been the potential for dispersal into neighbouring catchments. A fragment of the mtDNA CO1 gene was analysed and a Mantel test revealed a significant isolation by distance effect for both species. Significant overall FST values confirmed that both species exhibited low levels of dispersal, a prediction for populations inhabiting a fragmented upland environment. The level of structure in M. australiense is surprising for a widely distributed species. Not all M. australiense populations conformed to the stream-hierarchy model, with results being best explained by historical river realignment or cross-catchment dispersal. The fact that both species show limited dispersal highlights the importance of conservation in highland areas for both endemic and widely spread species.
Circular permutation of a synthetic eukaryotic chromosome with the telomerator
Authors: Mitchell Leslie A. , Boeke Jef D.
Published: November 2014

Significance

The ability to design and build nonnative DNA sequences conferring specific and useful engineered functions on cells defines the field of synthetic biology. Here, we describe a synthetic biology device built for
Saccharomyces cerevisiae.
The telomerator inducibly and precisely linearizes circular DNA molecules in vivo, yielding derivatives that encode functional telomeres at each end. The telomerator provides the means to engineer artificial chromosomes, typically constructed as circular molecules, because telomerator-mediated linearization permits specific positioning of genes to modulate their expression. The telomerator also provides a tool to probe spatial relationships between functional elements on chromosomes such as telomeres, centromeres, and replication origins. In the future, the telomerator may be applied to engineer artificial chromosomes in other organisms.
Go West: Georgia's European identity and its role in domestic politics and foreign policy objectives
Authors: Beacháin Donnacha Ó , Coene Frederik
Published: November 2014

This article sheds light on the Euro-Atlantic discourse in Georgia by situating it in a wider frame. It provides an analysis of its Euro-Atlantic orientation by presenting it as a continuation of past efforts to involve European powers in Georgian affairs and highlights changing trends in this aspect of contemporary foreign policy. Far from determining whether or not the Georgians are European, the different arguments that have been used to support Georgian “Europeanness” are evaluated to assess its role in the national identity construction process. Focusing primarily on the United National Movement government led by Mikheil Saakashvili, we demonstrate how the Euro-Atlantic discourse has been employed domestically by the political elite as a legitimacy management strategy and explore its function in seeking Western patronage, a key foreign policy goal.
Testing for linguistic injustice: territoriality and pluralism
Authors: Schutter Helder De
Published: November 2014

This article develops a linguistic injustice test. Language policy measures passing the test conflict with the normative ideal of equal language recognition. The first part of the test checks for external restrictions - language policies that grant more recognition to one language group than to another. The second part of the test checks for internal restrictions - language policies that grant more recognition to some members of a language group than to other members of the same group. The article then applies the linguistic injustice test to two models of linguistic justice: linguistic territoriality and linguistic pluralism. It is argued that real-life cases of linguistic territoriality tend to pass the test. It is argued that instantiations of linguistic pluralism tend to fail the test.
East China Sea or South China Sea, they are all China's Seas: comparing nationalism among China's maritime irredentist claims†
Authors: Dixon Jonathan
Published: November 2014

Much has been made over the past few years of China'vs ambitions of regaining control of its irredentist claims in the East and South China Seas. While some of this speculation focuses on the massive amounts of money the People's Republic of China (PRC) has funneled into its naval modernization program, other analysts are more interested in the drivers behind the increasingly popular sentiment that the country must “reclaim” its lost territories. The Chinese Communist Party can ill afford to ignore the voice of an already disenchanted population if it hopes to stay in power, particularly in regard to matters of national pride. As a result, in dealing with China's irredentist claims, nationalism in particular can be a powerful ideological factor in shaping the nation's foreign policies. This is especially apparent in the case of irredentism, where nationalism can often override diplomatic and strategic imperatives. This paper addresses the question of how does the nationalist discourse vary between two territorial disputes, the East and South China Seas. It uses discourse analysis to examine developing trends among online social media and news sites. This in turn allows for the construction of a framework of how nationalism develops among both elite and grassroots audiences.
Pulmonary Arterial Hypertension in a Patient with Cowden Syndrome and the PTEN Mutation
Authors: Ha Duc , Mester Jessica , Eng Charis , Farha Samar
Published: November 2014

The pathogenesis of pulmonary arterial hypertension (PAH) exhibits many neoplastic‐like features. Cowden syndrome is a difficult‐to‐recognize heritable cancer syndrome caused by a germline mutation in the phosphatase‐and‐tensin homolog deleted on the chromosome 10 (PTEN) gene. PTEN regulation has been implicated in cancer development and, more recently, PAH pathogenesis. Here we report a case of PAH in a patient with Cowden syndrome and the response to pulmonary vasodilators.
Racial Differences in Abnormal Ambulatory Blood Pressure Monitoring Measures: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Muntner Paul , Lewis Cora E. , Diaz Keith M. , Carson April P. , Kim Yongin , Calhoun David , Yano Yuichiro , Viera Anthony J. , Shimbo Daichi
Published: November 2014

BACKGROUND

Several ambulatory blood pressure monitoring (ABPM) measures have been associated with increased cardiovascular disease risk independent of clinic blood pressure (BP). African Americans have higher clinic BP compared with Whites but few data are available on racial differences in ABPM measures.

METHODS

We compared ABPM measures between African American (n = 178) and White (n = 103) participants at the Year 5 Coronary Artery Risk Development in Young Adults study visit. BP was measured during a study visit and the second and third measurements were averaged. ABPM was conducted over the following 24 hours.

RESULTS

Mean ± SD age of participants was 29.8±3.8 years and 30.8±3.5 years for African Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD 1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after age–gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among African Americans compared with Whites (P < 0.001). After multivariable adjustment, the African Americans were more likely than Whites to have nocturnal hypertension (prevalence ratio: 2.44, 95% CI: 0.99–6.05) and nondipping (prevalence ratio: 2.50, 95% CI: 1.39–4.48). The prevalence of masked hypertension among African Americans and Whites was 4.4% and 2.1%, respectively, (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P = 0.99). Twenty-four hour BP variability on ABPM was higher among African Americans compared with Whites.

CONCLUSIONS

These data suggest racial differences in several ABPM measures exist.
ALD1 Regulates Basal Immune Components and Early Inducible Defense Responses in Arabidopsis
Authors: Cecchini Nicolás M. , Jung Ho Won , Engle Nancy L. , Tschaplinski Timothy J. , Greenberg Jean T.
Published: November 2014

Robust immunity requires basal defense machinery to mediate timely responses and feedback cycles to amplify defenses against potentially spreading infections. AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) is needed for the accumulation of the plant defense signal salicylic acid (SA) during the first hours after infection with the pathogen Pseudomonas syringae and is also upregulated by infection and SA. ALD1 is an aminotransferase with multiple substrates and products in vitro. Pipecolic acid (Pip) is an ALD1-dependent bioactive product induced by P. syringae. Here, we addressed roles of ALD1 in mediating defense amplification as well as the levels and responses of basal defense machinery. ALD1 needs immune components PAD4 and ICS1 (an SA synthesis enzyme) to confer disease resistance, possibly through a transcriptional amplification loop between them. Furthermore, ALD1 affects basal defense by controlling microbial-associated molecular pattern (MAMP) receptor levels and responsiveness. Vascular exudates from uninfected ALD1-overexpressing plants confer local immunity to the wild type and ald1 mutants yet are not enriched for Pip. We infer that, in addition to affecting Pip accumulation, ALD1 produces non-Pip metabolites that play roles in immunity. Thus, distinct metabolite signals controlled by the same enzyme affect basal and early defenses versus later defense responses, respectively.
Pseudozyma aphidisInduces Salicylic-Acid-Independent Resistance toClavibacter michiganensisin Tomato Plants
Authors: Barda Omer , Shalev Or , Alster Shanee , Buxdorf Kobi , Gafni Aviva , Levy Maggie
Published: November 2014

The ability of plant pathogens to rapidly develop resistance to commonly used pesticides challenges efforts to maximize crop production. Fungal biocontrol agents have become an important alternative to chemical fungicides as a result of environmental concerns regarding conventional pesticides, including resistance issues. The complex mode of action of biocontrol agents reduces the likelihood that pathogens will develop resistance to them. We recently isolated a unique, biologically active isolate of the epiphytic fungus Pseudozyma aphidis. We show that the extracellular metabolites secreted by our P. aphidis isolate can inhibit Xanthomonas campestris pv. vesicatoria, X. campestris pv. campestris, Pseudomonas syringae pv. tomato, Erwinia amylovora, Clavibacter michiganensis, and Agrobacterium tumefaciens in vitro. Moreover, application of Pseudozyma aphidis spores on tomato plants in the greenhouse significantly reduced (by 60%) the incidence of bacterial wilt and canker disease caused by C. michiganensis subsp. michiganensis on those plants as well as disease severity by 35%. Furthermore, infected plants treated with P. aphidis were 25% taller than control infected plants. We found that P. aphidis activates PR1a—and other pathogenesis-related genes in tomato plants—and can trigger an induced-resistance response against C. michiganensis that proceeds in a salicylic-acid-independent manner, as shown using NahG-transgenic tomato plants.
First Report of Cherry Stem Rot and Leaf Necrosis Disease Caused by Phytophthora nicotianae in Yantai, China
Authors: Yu X. L. , Liu X. Q. , Wang P. S. , Wang Y. Z.
Published: November 2014

Cherry (Cerasus avium (Linn.) Moench) is the third most economically important fruit in Yantai, Shandong Province, China. In August 2012, brown spots or necrosis on cherry seedling leaves, with an incidence of 8.2 to 34.3%, were observed in some fields of cherry seedlings in Yantai. Our survey indicated that the economic losses could reach up to 15.3% if disease conditions, such as a cool rainy summer season, were favorable. Conspicuous watery lesions on the stems turned to brown streaks; the leaves all wilted; and finally the plants collapsed. Diseased stem and leaf samples were surface-disinfected in 1% sodium hypochlorite for 1 min, rinsed three times in sterile water, which was absorbed with filter paper, and then transferred to 10% V8 juice agar medium containing 50 μg/ml ampicillin and 5 μg/ml carbendazim (1). The plates were incubated at 22°C in the dark for 5 days. The colonies consisted of white, loose, fluffy aerial mycelia. Eight isolates were obtained, and all were identified as Phytophthora nicotianae based on morphological characteristics and the sequence of the internal transcribed spacer (ITS) region of rDNA. The sporangia were ovoid/spherical, obturbinate with rounded bases and prominent papillae that were 37.5 to 62.5 × 30 to 50 μm (average 46.4 × 37.8 μm, n = 100) in size, with an average length-to-breadth ratio of 1.2. Chlamydospores were terminal, intercalary, and measured 19 to 42 μm (average 30.4 μm), which is typical of P. nicotianae (2). The genomic DNA of the eight isolates was extracted from mycelia. The ITS region of all eight isolates was amplified using primers ITS1 and ITS4, producing specific products that were directly sequenced. The sequence of a representative isolate P1401 (895 bp) was submitted to GenBank (Accession No. KJ754387). It was 100% similar to P. nicotianae strains NV-20T and TARI 22073 (KC768775 and GU111667). To confirm the pathogenicity, at least 10 cherry leaves and new stems were inoculated with mycelial plugs (5 × 5 mm) from each isolate. Necrosis of leaves and stems was observed 4 and 7 days after inoculation, respectively. No symptoms were observed on the control leaves and stems that were inoculated with blank agar plugs. P. nicotianae was re-isolated from the infected leaves, and the ITS sequence was analyzed to confirm its identity. Phytophthora species, such as P. cambivora, P. megasperma, and P. drechsleri, had been previously isolated from cherry (3), but to the best of our knowledge this is the first report of stem rot and leaf necrosis disease caused by P. nicotianae on cherry. Since the economic loss caused by this disease could reach 15% if an outbreak occurred in a rainy summer, control measures should be implemented.

References: (1) Y. Balci et al. Mycol. Res. 112:906, 2008. (2) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St Paul, MN, 1996. (2) S. M. Mircetich and M. E. Matheron. Phytopathology 66:549, 1976.
The Influence of Irrigation Frequency on the Onset and Development of Verticillium Wilt of Olive
Authors: Pérez-Rodríguez M. , Alcántara E. , Amaro M. , Serrano N. , Lorite I. J. , Arquero O. , Orgaz F. , López-Escudero F. J.
Published: November 2014

The influence of irrigation frequency on the onset and development of Verticillium wilt of olive (VWO) was studied. A split-plot design in microplots with naturally infested soil was established for studying four irrigation frequencies for three olive cultivars with differing levels of disease resistance. Final disease incidence (DI) and mortality in ‘Picual’ plants subjected to daily irrigation treatment (T1) reached values of 100 and 63%, respectively. For Picual-T1 samples, the area under the disease progress curve values were significantly different between 15 December 2012 and 15 July 2013 (14.8 to 42.8%) compared with the average results of the other treatments, which were weekly (T2), biweekly (T3), and deficit (T4) (0.4 to 11.5%). No significant differences between the irrigation treatments were observed in ‘Arbequina’, although the DI progressed consistently (60% in all treatments). In ‘Frantoio’, little disease developed. We conclude that a daily irrigation treatment encourages VWO development in susceptible Picual. Therefore, in susceptible cultivars growing in infested soils under daily irrigation regimes, the extension of irrigation frequency may reduce disease incidence. In the context of an integrated control, the use of resistant cultivars seems to be more relevant than the detrimental effects observed in frequent irrigation schedules.
Postoperative Bladder Catheterization Based on Individual Bladder Capacity
Authors: Brouwer Tammo A. , Rosier Peter F. W. M. , Moons Karel G. M. , Zuithoff Nicolaas P. A. , van Roon Eric N. , Kalkman Cor J.
Published: November 2014

Background:

Untreated postoperative urinary retention can result in permanent lower urinary tract dysfunction and can be prevented by timely bladder catheterization. The author hypothesized that the incidence of postoperative bladder catheterization can be decreased by using the patient’s own maximum bladder capacity (MBC) instead of a fixed bladder volume of 500 ml as a threshold for catheterization.

Methods:

Randomized parallel-arm and single-blinded comparative effectiveness trial conducted in 1,840 surgical patients, operated under general or spinal anesthesia without an indwelling urinary catheter. Patients were randomized to either use their individual MBC (index) or a fixed bladder volume of 500 ml (control) as a threshold for postoperative bladder catheterization. Preoperatively, the MBC was determined at home by voiding in a calibrated bowl. All other bladder volumes were measured by ultrasound. Postoperatively, bladder catheterization was performed when spontaneous voiding was impossible, and the ultrasound measurement exceeded the threshold for the group in which the patient was randomized (500 or MBC). The primary outcome was the incidence of bladder catheterization.

Results:

The average MBC in the control group was 582 ml (±199 ml) and in the index group 611 ml (±209 ml). The incidence of catheterization decreased from 11.8% (107 of 909 patients) in the control group to 8.6% (80 of 931) in the index group (relative risk 0.73, 95% CI 0.55 to 0.96, P = 0.025). There were no adverse events in either group.

Conclusions:

In patients undergoing surgery under general or spinal anesthesia using the MBC rather than a fixed 500 ml threshold for bladder catheterization is a safe approach that significantly reduces the incidence of postoperative bladder catheterizations.
Effect of Minocycline on Lumbar Radicular Neuropathic Pain
Authors: Vanelderen Pascal , Van Zundert Jan , Kozicz Tamás , Puylaert Martine , De Vooght Pieter , Mestrum Roel , Heylen René , Roubos Eric , Vissers Kris
Published: November 2014

AbstractAbstract

In a controlled trial of 60 patients with subacute lumbar radicular pain, a 2-week treatment with minocycline or amitriptyline reduced pain compared to placebo. Reductions in pain over this short time period were small and unlikely to be clinically significant.

Background:

Less than 50% of patients experience sufficient pain relief with current drug therapy for neuropathic pain. Minocycline shows promising results in rodent models of neuropathic pain but was not studied in humans with regard to the treatment of neuropathic pain.

Methods:

In this randomized, double-blind, placebo-controlled clinical trial, patients with subacute lumbar radicular pain received placebo, amitriptyline 25 mg, or minocycline 100 mg once a day (n = 20 per group) for 14 days. Primary outcome measure was the pain intensity in the leg as measured by a numeric rating scale ranging from 0 to 10 on days 7 and 14. Secondary outcome measures were the reduction of neuropathic pain symptoms in the leg as determined with a neuropathic pain questionnaire, consumption of rescue medication, and adverse events on days 7 and 14.

Results:

Sixty patients were randomized and included in an intention-to-treat analysis. After 14 days, patients in the minocycline and amitriptyline groups reported a reduction of 1.47 (95% confidence interval, 0.16–2.83; P = 0.035) and 1.41 (95% confidence interval, 0.05–2.78; P = 0.043), respectively, in the numeric rating scale compared to the placebo group. No differences were seen in the neuropathic pain questionnaire values at any time point during treatment between the three groups. The rate of adverse events in the amitriptyline group was 10% versus none in the minocycline and placebo groups. No differences were noted in the consumption of rescue medication.

Conclusions:

Although both groups differed from placebo, their effect size was small and therefore not likely to be clinically meaningful.
Self-referrals in a Dutch Emergency Department: how appropriate are they?
Authors: Kraaijvanger Nicole , Rijpsma Douwe , van Leeuwen Henk , van Dijk Nadine , Edwards Michael
Published: November 2014

Objective

Self-referred visits account for an average of 30% of all Emergency Department (ED) visits in the Netherlands. Some of these are considered inappropriate, because patients receive care that a GP can provide. Worldwide, studies have used various methods to determine the proportion of inappropriate visits by self-referred patients, resulting in diverging percentages. The aim of this study was to find a reliable percentage of appropriate visits to the ED by self-referred patients in the Netherlands.

Methods

This observational, prospective study was performed in the ED of a hospital in the Netherlands. Data were collected on all self-referred patients in four separate months over 1 year. The appropriateness of an ED visit was determined at two time points: first, after primary assessment of the patient, using predefined criteria, and second the moment the patient left the ED, on the basis of the diagnosis and treatment received. Finally, the perspective of the patients was taken into account using a questionnaire.

Results

In 4 months 3196 self-referred patients were included. In all, 1862 (58.8%) visits were classified as appropriate according to the predefined criteria. When the second time point was taken into consideration, 48.1% of the patients had a secondary care diagnosis and/or needed secondary care treatment, classifying their visits as appropriate. According to the opinion of the patients 76.7% classified their visit as appropriate.

Conclusion

The percentage of appropriate ED visits by self-referred patients in the Netherlands ranges from 48.1 to 58.8%, as determined using two different methods.
Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain
Authors: Stachtari Chrysoula C. , Thomareis Olympia N. , Tsaousi Georgia G. , Karakoulas Konstantinos A. , Chatzimanoli Foteini I. , Chatzopoulos Stavros A. , Vasilakos Dimitrios G.
Published: November 2014

The aim of this study was to elucidate the antinociceptive interaction between cannabinoids and tramadol and their impact on proinflammatory response, in terms of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model of incisional pain. Prospective randomized trial assessing the individual or combined application of intraperitoneal tramadol (10 mg/kg) and the selective cannabinoid-2 (CB-2) agonist (R,S)-AM1241 (1 mg/kg) applied postsurgical stress stimulus. Pharmacological specificity was established by antagonizing tramadol with naloxone (0.3 mg/kg) and (R,S)-AM1241 with SR144528 (1 mg/kg). Thermal allodynia was assessed by hot plate test 30 (T30), 60 (T60), and 120 (T120) minutes after incision. Blood samples for plasma IL-6 and IL-2 level determination were obtained 2 hours after incision. Data from 42 rats were included in the final analyses. Significant augmentation of thermal threshold was observed at all time points, after administration of either tramadol or (R,S)-AM1241 compared with the control group (P = 0.004 and P = 0.015, respectively). The combination of (R,S)-AM1241 plus tramadol promoted the induced antinociception in an important manner compared with control (P = 0.002) and (R,S)-AM1241 (P = 0.022) groups. Although the antiallodynic effect produced by tramadol was partially reversed by naloxone 30 and 60 minutes after incision (P = 0.028 and P = 0.016, respectively), SR144528 blocked the effects of (R,S)-AM1241 administration in a significant manner (P = 0.001) at all time points. Similarly, naloxone plus SR144528 also blocked the effects of the combination of (R,S)-AM1241 with tramadol at all time points (P = 0.000). IL-6 level in (R,S)-AM1241 plus tramadol group was significantly attenuated compared with control group (P = 0.000). Nevertheless, IL-2 levels remained unchanged in all experimental groups. It seems that the concomitant administration of a selective CB-2 agonist with tramadol in incisional pain model may improve antinociceptive effects and immune responses of cannabinoids, but this effect does not seem to be superior to that of tramadol alone.
Gastroesophageal Reflux in Young Children and Adolescents
Authors: Quitadamo Paolo , Di Nardo Giovanni , Miele Erasmo , Campione Severo , Mancusi Valeria , Oliva Salvatore , Rossi Paolo , Tiberti Antonio , Staiano Annamaria , D'Armiento Maria
Published: November 2014

Background:

The pediatric literature about the correlation between symptoms and histological lesions in patients investigated for gastroesophageal reflux disease is scarce and inconclusive. The primary aim of the present study was to assess the relation between the complained symptom severity and the esophageal histological grade, through the use of validated and reliable scores.

Methods:

All children ages between 2 and 17 years referred to perform upper gastrointestinal endoscopy because of gastroesophageal reflux disease symptoms were asked to complete the Pediatric Gastroesophageal Symptom and Quality of Life validated questionnaire, investigating the main symptoms complained and their impact on daily life and school activities. Esophageal mucosal samples taken during the procedure were analyzed and scored according to the Yerian‐Fiocca classification.

Results:

A total of 164 children were included in the study. No significant association was found between symptomatic score and histological score (rs: 0.05, P: 0.49). Even when focusing only on adolescents with heartburn or chest pain, no correlation between symptom severity and esophageal lesions was found (rs: −0.18, P: 0.264). Intercellular space diameter values did not mirror symptom severity.

Conclusions:

The main finding of this study on children with reflux symptoms is the lack of correlation between symptom severity and esophageal histological grade. The magnitude of intercellular spaces was found not to be related with the clinical score as well.
Surgery and Postoperative Recurrence in Children With Crohn Disease
Authors: Hansen Lars F. , Jakobsen Christian , Paerregaard Anders , Qvist Niels , Wewer Vibeke
Published: November 2014

Objectives:

The aim of this study was to describe surgery rates, complications, and risk of disease recurrence after surgery in paediatric Crohn disease (CD).

Methods:

Children <18 years with a diagnosis of CD and a least 1 intestinal resection from the period January 1, 1978 to December 31, 2007 were identified using the Danish National Patient Registry. Patient charts were used to extract data.

Results:

A total of 115 of 422 children with CD, who had surgery in 2 referral centres, were further studied. Disease extension according to the Montreal classification at the time of operation was available in 106/115 patients: B1, 39/106 (37%); B2, 59/106 (56%); and B3, 8/106 (7%). Before/after surgery 89%/36% of the patients received corticosteroids, 26%/61% azathioprine, and 15%/34% infliximab. Ileocoecal resection was performed in 54 (47%); 17 (15%) underwent ileal resection, 21 (18%) colectomy, 13 (11%) hemicolectomy, and 10 (9%) a combined colonic and ileal resection. Median time from diagnosis to surgery was 23 months (range 0–147). The median follow‐up time after surgery was 121 months (16–226), and median time to disease recurrence was 12 months (3–160). The cumulative clinical recurrence rates at 1, 5, and 10 years were 50%, 73%, and 77%, respectively. More than 1 bowel resection was needed in 39%. Postoperative azathioprine treatment did not affect rate of recurrence after surgery.

Conclusions:

In this large cohort of children with CD studied for >10 years postoperatively, we found a high postoperative recurrence rate of disease and a frequent need for >1 intestinal resection.
Clinical Features of Interleukin 10 Receptor Gene Mutations in Children With Very Early–Onset Inflammatory Bowel Disease
Authors: Beser Omer F. , Conde Cecilia Dominguez , Serwas Nina K. , Cokugras Fügen Cullu , Kutlu Tufan , Boztug Kaan , Erkan Tulay
Published: November 2014

Objectives:

In the present study, we studied a cohort of patients with very early onset inflammatory bowel disease (IBD) to determine the frequency of mutations in the interleukin 10 (IL10) receptor genes as a cause of early‐onset IBD.

Methods:

Sanger sequencing was performed to determine the presence of IL10 and/or IL10 receptor mutations in 17 patients with a diagnosis of very early onset IBD (disease onset <2 years of age in 15 patients, between 3 and 4 years in the other 2). Mutation screening was performed including all of the coding regions of the IL10, IL10RA, and IL10RB genes. We then compared the follow‐up findings of the patients with IL10 receptor mutations in terms of demographic, clinical, laboratory, and treatment response properties with those of patients diagnosed as having very early onset IBD with no mutation.

Results:

We identified 3 patients bearing mutations in the IL10 or IL10 receptor genes, including 1 mutation in IL10RB that has been described recently (c.G477A, p.Trp159*) and 2 novel mutations affecting the IL10RA gene (c.T192G, p.Tyr64* and c.T133G, p.Trp45Gly). Collectively, these mutations thus provided genetic etiology for 17.6% of the cohort under investigation. The presence of a family history of IBD and the clinical course of Crohn disease differed between patients with mutations in the IL‐10 pathway and those without such mutations. Although perianal fistulas were found in all of the patients with IL10 receptor mutations, they were found in only 14.3% of those without such mutations. The lower values of weight‐for‐age and height‐for‐age z scores, necessity for more intensive therapy, achievement of longer periods until remission, and frequent relapses in the patients bearing mutations in the IL10 receptor genes all underlined the severity of the disease and its relatively poor response to treatment.

Conclusions:

In spite of the small number of patients with mutations affecting the IL‐10 signaling pathway in our study, in all of the patients with IL10 receptor mutations, the disease onset occurs at an early age, the prognosis is poor, and the response to treatment is insufficient.
Computerized Dose Range Checking Using Hard and Soft Stop Alerts Reduces Prescribing Errors in a Pediatric Intensive Care Unit
Authors: Balasuriya Lilanthi , Vyles David , Bakerman Paul , Holton Vanessa , Vaidya Vinay , Garcia-Filion Pamela , Westdorp Joan , Sanchez Christine , Kurz Rhonda
Published: November 2014

Objective

An enhanced dose range checking (DRC) system was developed to evaluate prescription error rates in the pediatric intensive care unit and the pediatric cardiovascular intensive care unit.

Methods

An enhanced DRC system incorporating “soft” and “hard” alerts was designed and implemented. Practitioner responses to alerts for patients admitted to the pediatric intensive care unit and the pediatric cardiovascular intensive care unit were retrospectively reviewed.

Results

Alert rates increased from 0.3% to 3.4% after “go-live” (P < 0.001). Before go-live, all alerts were soft alerts. In the period after go-live, 68% of alerts were soft alerts and 32% were hard alerts. Before go-live, providers reduced doses only 1 time for every 10 dose alerts. After implementation of the enhanced computerized physician order entry system, the practitioners responded to soft alerts by reducing doses to more appropriate levels in 24.7% of orders (70/283), compared with 10% (3/30) before go-live (P = 0.0701). The practitioners deleted orders in 9.5% of cases (27/283) after implementation of the enhanced DRC system, as compared with no cancelled orders before go-live (P = 0.0774). Medication orders that triggered a soft alert were submitted unmodified in 65.7% (186/283) as compared with 90% (27/30) of orders before go-live (P = 0.0067). After go-live, 28.7% of hard alerts resulted in a reduced dose, 64% resulted in a cancelled order, and 7.4% were submitted as written.

Conclusions

Before go-live, alerts were often clinically irrelevant. After go-live, there was a statistically significant decrease in orders that were submitted unmodified and an increase in the number of orders that were reduced or cancelled.
GC-content evolution in bacterial genomes: the biased gene conversion hypothesis expands
Authors: Lassalle Florent , Périan Séverine , Bataillon Thomas , Nesme Xavier , Duret Laurent , Daubin Vincent
Published: November 2014

The characterization of functional elements in genomes relies on the identification of the footprints of natural selection. In this quest, taking into account neutral evolutionary processes such as mutation and genetic drift is crucial because these forces can generate patterns that may obscure or mimic signatures of selection. In mammals, and probably in many eukaryotes, another such confounding factor called GC-Biased Gene Conversion (gBGC) has been documented. This mechanism generates patterns identical to what is expected under selection for higher GC-content, specifically in highly recombining genomic regions. Recent results have suggested that a mysterious selective force favouring higher GC-content exists in Bacteria but the possibility that it could be gBGC has been excluded. Here, we show that gBGC is probably at work in most if not all bacterial species. First we find a consistent positive relationship between the GC-content of a gene and evidence of intra-genic recombination throughout a broad spectrum of bacterial clades. Second, we show that the evolutionary force responsible for this pattern is acting independently from selection on codon usage, and could potentially interfere with selection in favor of optimal AU-ending codons. A comparison with data from human populations shows that the intensity of gBGC in Bacteria is comparable to what has been reported in mammals. We propose that gBGC is not restricted to sexual Eukaryotes but also widespread among Bacteria and could therefore be an ancestral feature of cellular organisms. We argue that if gBGC occurs in bacteria, it can account for previously unexplained observations, such as the apparent non-equilibrium of base substitution patterns and the heterogeneity of gene composition within bacterial genomes. Because gBGC produces patterns similar to positive selection, it is essential to take this process into account when studying the evolutionary forces at work in bacterial genomes.
A pedagogical walkthrough of computational modeling and simulation of Wnt signaling pathway using static causal models in Matlab
Authors: Sinha Shriprakash
Published: November 2014

A tutorial introduction to computational modeling of Wnt signaling pathway in a human colorectal cancer dataset using static Bayesian network models is provided. The walkthrough might aid bio-logists/informaticians in understanding the design of computational experiments that is interleaved with exposition of the Matlab code and causal models from Bayesian Network toolbox. This is done in order to ease the understanding of beginner students and researchers in transition to computational signaling biology, who intend to work in the field of modeling of signaling pathways. The manuscript expounds the computational flow of the contents in advance article1via code development and takes the reader in a step by step process of how • the collection and the transformation of the available biological information from literature is done, • the integration of the heterogeneous data and prior biological knowledge in the network is achieved, • conditional probability tables for nodes in biologically inspired tables are estimated, • the simulation study is designed, • the hypothesis regarding a biological phenomena is transformed into computational framework, and • results and inferences drawn usingd-connectivity/separability are reported. The manuscript finally ends with a programming assignment to help the readers get hands on experience of a perturbation project. Matlab code with dataset is made available under GNU GPL v3 license at google code project onhttps://code.google.com/p/static-bn-for-wnt-signaling-pathway

Insight, Innovation and Integration

Simulation study involving computational experiments dealing with Wnt signaling pathways abound in literature but often lack a pedagogical perspective that might ease the understanding of beginner students and researchers in transition who intend to work on modeling of the pathway. This paucity might happen due to restrictive policies which enforce an unwanted embargo on the sharing of important scientific knowledge. The manuscript elucidates embedding of prior biological knowledge, integration of heterogeneous information, transformation of biological hypothesis into computational framework and design of experiments in a simple manner interleaved with aspects of Bayesian Network toolbox and Matlab code so as to help readers get a feel of a project related to modeling of the pathway.
Large transcription units unify copy number variants and common fragile sites arising under replication stress
Authors: Wilson Thomas E. , Arlt Martin F. , Park So Hae , Rajendran Sountharia , Paulsen Michelle , Ljungman Mats , Glover Thomas W.
Published: November 2014

Copy number variants (CNVs) resulting from genomic deletions and duplications and common fragile sites (CFSs) seen as breaks on metaphase chromosomes are distinct forms of structural chromosome instability precipitated by replication inhibition. Although they share a common induction mechanism, it is not known how CNVs and CFSs are related or why some genomic loci are much more prone to their occurrence. Here we compare large sets of de novo CNVs and CFSs in several experimental cell systems to each other and to overlapping genomic features. We first show that CNV hotpots and CFSs occurred at the same human loci within a given cultured cell line. Bru-seq nascent RNA sequencing further demonstrated that although genomic regions with low CNV frequencies were enriched in transcribed genes, the CNV hotpots that matched CFSs specifically corresponded to the largest active transcription units in both human and mouse cells. Consistently, active transcription units >1 Mb were robust cell-type-specific predictors of induced CNV hotspots and CFS loci. Unlike most transcribed genes, these very large transcription units replicated late and organized deletion and duplication CNVs into their transcribed and flanking regions, respectively, supporting a role for transcription in replication-dependent lesion formation. These results indicate that active large transcription units drive extreme locus- and cell-type-specific genomic instability under replication stress, resulting in both CNVs and CFSs as different manifestations of perturbed replication dynamics.
Large-scale genomic sequencing of extraintestinal pathogenic Escherichia coli strains
Authors: Salipante Stephen J. , Roach David J. , Kitzman Jacob O. , Snyder Matthew W. , Stackhouse Bethany , Butler-Wu Susan M. , Lee Choli , Cookson Brad T. , Shendure Jay
Published: November 2014

Large-scale bacterial genome sequencing efforts to date have provided limited information on the most prevalent category of disease: sporadically acquired infections caused by common pathogenic bacteria. Here, we performed whole-genome sequencing and de novo assembly of 312 blood- or urine-derived isolates of extraintestinal pathogenic (ExPEC) Escherichia coli, a common agent of sepsis and community-acquired urinary tract infections, obtained during the course of routine clinical care at a single institution. We find that ExPEC E. coli are highly genomically heterogeneous, consistent with pan-genome analyses encompassing the larger species. Investigation of differential virulence factor content and antibiotic resistance phenotypes reveals markedly different profiles among lineages and among strains infecting different body sites. We use high-resolution molecular epidemiology to explore the dynamics of infections at the level of individual patients, including identification of possible person-to-person transmission. Notably, a limited number of discrete lineages caused the majority of bloodstream infections, including one subclone (ST131-H30) responsible for 28% of bacteremic E. coli infections over a 3-yr period. We additionally use a microbial genome-wide-association study (GWAS) approach to identify individual genes responsible for antibiotic resistance, successfully recovering known genes but notably not identifying any novel factors. We anticipate that in the near future, whole-genome sequencing of microorganisms associated with clinical disease will become routine. Our study reveals what kind of information can be obtained from sequencing clinical isolates on a large scale, even well-characterized organisms such as E. coli, and provides insight into how this information might be utilized in a healthcare setting.
Malate Synthesis and Secretion Mediated by a Manganese-Enhanced Malate Dehydrogenase Confers Superior Manganese Tolerance in Stylosanthes guianensis
Authors: Chen Zhijian , Sun Lili , Liu Pandao , Liu Guodao , Tian Jiang , Liao Hong
Published: November 2014

Manganese (Mn) toxicity is a major constraint limiting plant growth on acidic soils. Superior Mn tolerance in Stylosanthes spp. has been well documented, but its molecular mechanisms remain largely unknown. In this study, superior Mn tolerance in Stylosanthes guianensis was confirmed, as reflected by a high Mn toxicity threshold. Furthermore, genetic variation of Mn tolerance was evaluated using two S. guianensis genotypes, which revealed that the Fine-stem genotype had higher Mn tolerance than the TPRC2001-1 genotype, as exhibited through less reduction in dry weight under excess Mn, and accompanied by lower internal Mn concentrations. Interestingly, Mn-stimulated increases in malate concentrations and exudation rates were observed only in the Fine-stem genotype. Proteomic analysis of Fine-stem roots revealed that S. guianensis Malate Dehydrogenase1 (SgMDH1) accumulated in response to Mn toxicity. Western-blot and quantitative PCR analyses showed that Mn toxicity resulted in increased SgMDH1 accumulation only in Fine-stem roots, but not in TPRC2001-1. The function of SgMDH1-mediated malate synthesis was verified through in vitro biochemical analysis of SgMDH1 activities against oxaloacetate, as well as in vivo increased malate concentrations in yeast (Saccharomyces cerevisiae), soybean (Glycine max) hairy roots, and Arabidopsis (Arabidopsis thaliana) with SgMDH1 overexpression. Furthermore, SgMDH1 overexpression conferred Mn tolerance in Arabidopsis, which was accompanied by increased malate exudation and reduced plant Mn concentrations, suggesting that secreted malate could alleviate Mn toxicity in plants. Taken together, we conclude that the superior Mn tolerance of S. guianensis is achieved by coordination of internal and external Mn detoxification through malate synthesis and exudation, which is regulated by SgMDH1 at both transcription and protein levels.
Two ammonium tetrachloridoaluminate salts: how a twinned orthorhombic structure emulates a trigonal crystal system
Authors: Tillmann Jan , Lerner Hans-Wolfram , Bolte Michael
Published: November 2014

We have determined the crystal structures of two tetrachloridoaluminate salts. Tetrabutylammonium tetrachloridoaluminate benzene hemisolvate, (C16H36N)[AlCl4]·0.5C6H6, (I), crystallizes with discrete cations, anions and solvent molecules. The benzene molecule is located on a centre of inversion. The structure of the benzene-free polymorph has been determined previously. Tetraethylammonium tetrachloridoaluminate, (C8H20N)[AlCl4], (II), also crystallizes with discrete cations and anions, and forms crystals which appear trigonal but are actually orthorhombic. With the additional reflections of the second and third domains of this nonmerohedral twin, a trigonal lattice is emulated, although the correct crystal system is orthorhombic.
Two ZnIImononuclear coordination compounds with pyridinedicarboxylate and auxiliaryN-(pyridin-4-ylmethylidene)hydroxylamine ligands
Authors: Coropceanu Eduard B. , Dreab Ana , Croitor Lilia
Published: November 2014

Two new mononuclear coordination compounds, bis{4-[(hydroxyimino)methyl]pyridinium} diaquabis(pyridine-2,5-dicarboxylato-κ2N,O2)zincate(II), (C6H7N2O)2[Zn(C7H3NO4)2(H2O)2], (1), and (pyridine-2,6-dicarboxylato-κ3O2,N,O6)bis[N-(pyridin-4-ylmethylidene-κN)hydroxylamine]zinc(II), [Zn(C7H3NO4)(C6H6N2O)2], (2), have been synthesized and characterized by single-crystal X-ray diffractometry. The centrosymmetric ZnIIcation in (1) is octahedrally coordinated by two chelating pyridine-2,5-dicarboxylate ligands and by two water molecules in a distorted octahedral geometry. In (2), the ZnIIcation is coordinated by a tridentate pyridine-2,6-dicarboxylate dianion and by twoN-(pyridin-4-ylmethylidene)hydroxylamine molecules in a distortedC2-symmetric trigonal bipyramidal coordination geometry.
7-Cyclopropyl-2′-deoxytubercidin: a carbocyclic side-chain derivative of 7-deaza-2′-deoxyadenosine
Authors: Yang Haozhe , Budow-Busse Simone , Eickmeier Henning , Reuter Hans , Seela Frank
Published: November 2014

The title compound {systematic name: 4-amino-5-cyclopropyl-7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine}, C14H18N4O3, exhibits anantiglycosylic bond conformation, with the torsion angle χ = −108.7 (2)°. The furanose group shows a twisted C1′-exosugar pucker (S-type), withP= 120.0 (2)° and τm= 40.4 (1)°. The orientation of the exocyclic C4′—C5′ bond is -ap(trans), with the torsion angle γ = −167.1 (2)°. The cyclopropyl substituent points away from the nucleobase (antiorientation). Within the three-dimensional extended crystal structure, the individual molecules are stacked and arranged into layers, which are highly ordered and stabilized by hydrogen bonding. The O atom of the exocyclic 5′-hydroxy group of the sugar residue acts as an acceptor, forming a bifurcated hydrogen bond to the amino groups of two different neighbouring molecules. By this means, four neighbouring molecules form a rhomboidal arrangement of two bifurcated hydrogen bonds involving two amino groups and two O5′ atoms of the sugar residues.
Two drimane lactones, valdiviolide and 11-epivaldiviolide, in the form of a 1:1 cocrystal obtained fromDrimys winteriextracts
Authors: Paz Robles Cristian , Mercado Darío , Suarez Sebastián , Baggio Ricardo
Published: November 2014

A cocrystal, C15H22O3·C15H22O3, (I), obtained fromDrimys winteri, is composed of two isomeric drimane sesquiterpene lactones, namely valdiviolide, (Ia), and 11-epivaldiviolide, (Ib), neither of which has been reported in the crystal form. Both diastereoisomers present three chiral centres at sites 5, 10 and 11, with anSSRsequence in (Ia) and anSSSsequence in (Ib). O—H...O hydrogen bonds bind molecules into chains running along [\overline{1}20] and the chains are in turn linked by π–π stacking interactions to define planar weakly interacting arrays parallel to (001).