bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent approaches in screening methodology for drought resistance.
Authors: Nakhforoosh A. , Adu-Gyamfi J. , Bodner G. , Grausgruber H.
Published: November 2013

Genetic progress in yield of staple crops is an urgent need in view of population growth. Predicted climate changes due to global warming necessitate that this progress is materialized in environments, which are affected more often by drought. Direct selection for yield under drought conditions is usually hampered by low heritability. Therefore, breeders rely on secondary traits with higher heritabilities to improve drought tolerance in agricultural crops. The present review gives an overview of methods that are applied for screening secondary traits. While for aboveground traits simple, reliable, fast, non-destructive and cost-effective methods that allow a high-throughput phenotyping are available, a bottleneck in drought research methods exists in the root zone, although there is evidence that roots are a key trait for superior drought avoidance. Still only few field screening techniques exist and most root screening is restricted to young plants and artificial growth media that limit inference to field grown adult plants. Spectral methods are identified as promising approach for both above- and belowground measurements and could bridge the gap between high throughput needs of breeding and complexity of plant physiological measurements.
No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis
Authors: Goris An , van Setten Jessica , Diekstra Frank , Ripke Stephan , Patsopoulos Nikolaos A. , Sawcer Stephen J. ,   The International Multiple Sclerosis Genetics Consortium, van Es Michael ,   The Australia and New Zealand MS Genetics Consortium, Andersen Peter M. , Melki Judith , Meininger Vincent , Hardiman Orla , Landers John E. , Brown Robert H. , Shatunov Aleksey , Leigh Nigel , Al-Chalabi Ammar , Shaw Christopher E. , Traynor Bryan J. , Chiò Adriano , Restagno Gabriella , Mora Gabriele , Ophoff Roel A. , Oksenberg Jorge R. , Van Damme Philip , Compston Alastair , Robberecht Wim , Dubois Bénédicte , van den Berg Leonard H. , De Jager Philip L. , Veldink Jan H. , de Bakker Paul I.W.
Published: November 2013

Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.
Dystrophic muscle improvement in zebrafish via increased heme oxygenase signaling
Authors: Kawahara Genri , Gasperini Molly J. , Myers Jennifer A. , Widrick Jeffrey J. , Eran Alal , Serafini Peter R. , Alexander Matthew S. , Pletcher Mathew T. , Morris Carl A. , Kunkel Louis M.
Published: November 2013

Duchenne muscular dystrophy (DMD) is caused by a lack of the dystrophin protein and has no effective treatment at present. Zebrafish provide a powerful in vivo tool for high-throughput therapeutic drug screening for the improvement of muscle phenotypes caused by dystrophin deficiency. Using the dystrophin-deficient zebrafish, sapje, we have screened a total of 2640 compounds with known modes of action from three drug libraries to identify modulators of the disease progression. Six compounds that target heme oxygenase signaling were found to rescue the abnormal muscle phenotype in sapje and sapje-like, while upregulating the inducible heme oxygenase 1 (Hmox1) at the protein level. Direct Hmox1 overexpression by injection of zebrafish Hmox1 mRNA into fertilized eggs was found to be sufficient for a dystrophin-independent restoration of normal muscle via an upregulation of cGMP levels. In addition, treatment of mdx5cv mice with the PDE5 inhibitor, sildenafil, which was one of the six drugs impacting the Hmox1 pathway in zebrafish, significantly increased the expression of Hmox1 protein, thus making Hmox1 a novel target for the improvement of dystrophic symptoms. These results demonstrate the translational relevance of our zebrafish model to mammalian models and support the use of zebrafish to screen for new drugs to treat human DMD. The discovery of a small molecule and a specific therapeutic pathway that might mitigate DMD disease progression could lead to significant clinical implications.
Transcription factor abundance controlled by an auto-regulatory mechanism involving a transcription start site switch
Authors: Ngondo Richard Patryk , Carbon Philippe
Published: November 2013

A transcriptional feedback loop is the simplest and most direct means for a transcription factor to provide an increased stability of gene expression. In this work performed in human cells, we reveal a new negative auto-regulatory mechanism involving an alternative transcription start site (TSS) usage. Using the activating transcription factor ZNF143 as a model, we show that the ZNF143 low-affinity binding sites, located downstream of its canonical TSS, play the role of protein sensors to induce the up- or down-regulation of ZNF143 gene expression. We uncovered that the TSS switch that mediates this regulation implies the differential expression of two transcripts with an opposite protein production ability due to their different 5′ untranslated regions. Moreover, our analysis of the ENCODE data suggests that this mechanism could be used by other transcription factors to rapidly respond to their own aberrant expression level.
Heterochromatin establishment at pericentromeres depends on nuclear position
Authors: Jachowicz Joanna W. , Santenard Angèle , Bender Ambre , Muller Julius , Torres-Padilla Maria-Elena
Published: November 2013

Mammalian development begins with fertilization of an oocyte by the sperm followed by genome-wide epigenetic reprogramming. This involves de novo establishment of chromatin domains, including the formation of pericentric heterochromatin. We dissected the spatiotemporal kinetics of the first acquisition of heterochromatic signatures of pericentromeric chromatin and found that the heterochromatic marks follow a temporal order that depends on a specific nuclear localization. We addressed whether nuclear localization of pericentric chromatin is required for silencing by tethering it to the nuclear periphery and show that this results in defective silencing and impaired development. Our results indicate that reprogramming of pericentromeric heterochromatin is functionally linked to its nuclear localization.
The Npl3 hnRNP prevents R-loop-mediated transcription–replication conflicts and genome instability
Authors: Santos-Pereira José M. , Herrero Ana B. , García-Rubio María L. , Marín Antonio , Moreno Sergio , Aguilera Andrés
Published: November 2013

Transcription is a major obstacle for replication fork (RF) progression and a cause of genome instability. Part of this instability is mediated by cotranscriptional R loops, which are believed to increase by suboptimal assembly of the nascent messenger ribonucleoprotein particle (mRNP). However, no clear evidence exists that heterogeneous nuclear RNPs (hnRNPs), the basic mRNP components, prevent R-loop stabilization. Here we show that yeast Npl3, the most abundant RNA-binding hnRNP, prevents R-loop-mediated genome instability. npl3Δ cells show transcription-dependent and R-loop-dependent hyperrecombination and genome-wide replication obstacles as determined by accumulation of the Rrm3 helicase. Such obstacles preferentially occur at long and highly expressed genes, to which Npl3 is preferentially bound in wild-type cells, and are reduced by RNase H1 overexpression. The resulting replication stress confers hypersensitivity to double-strand break-inducing agents. Therefore, our work demonstrates that mRNP factors are critical for genome integrity and opens the option of using them as therapeutic targets in anti-cancer treatment.
Poly[μ3-aqua-aqua-μ5-(4-nitrobenzoato)-caesium]
Authors: Smith Graham
Published: November 2013

In the structure of the title complex, [Cs(C7H4NO2)(H2O)2]n, the caesium salt of 4-nitrobenzoic acid, the irregular CsO9coordination sphere comprises three bridging nitro O-atom donors, a bidentate carboxylateO,O′-chelate interaction, a triple-bridging water molecule and a monodentate water molecule. A three-dimensional framework polymer is generated, within which there are water–carboxylate O—H...O and water–water O—H...O hydrogen-bonding interactions.
Bis(4-aminopyridinium) μ6-oxido-dodeca-μ2-oxido-hexaoxido[rhenium(VII)tetratungsten(VI)vanadium(V)]ate heptahydrate
Authors: Maaloui Ahlem , Toumi Samah Akriche , Rzaigui Mohamed
Published: November 2013

In the title organic–inorganic hybrid compound, (C5H7N2)2[ReVW4O19]·7H2O, the Lindqvist-type polyoxido anion has crystallographically imposedmm2 symmetry and is built up by sixMO6(M= W, V, Re) edge-sharing distorted octahedra. The Re and V atoms share the same crystallographic site in a 0.5:0.5 ratio. The 4-aminopyridinium cations lie on a mirror plane. Three of the four independent water O atoms in the asymmetric unit are located on a mirror plane whereas the remaining O atom hasmm2 site symmetry. In the crystal, the cations, anions and water molecules are linked into a three-dimensional network through O—H...O and N—H...O hydrogen-bonding interactions.
Imidazoliumtrans-diaquadioxalatochromate(III) dihydrate
Authors: Chérif Ichraf , Abdelhak Jawher , Zid Mohamed Faouzi , Driss Ahmed
Published: November 2013

In the title hydrated molecular salt, (C3H5N2)[Cr(C2O4)2(H2O)2]·2H2O, the complete cation is generated by a crystallographic twofold rotation axis, with one C atom lying on the rotation axis. The complete anion is generated by crystallographic inversion symmetry (CrIIIsite symmetry -1), to generate a slightly distorted CrO6octahedron withtranswater molecules and chelating oxalate dianions. The oxalate ion is almost planar (r.m.s. deviation = 0.017 Å) and the five-membered chelate ring is a shallow envelope with the metal ion displaced by 0.126 (1) Å from the ligand atoms. The crystal structure features O—H...O, N—H...O and C—H...O hydrogen bonds, which link the components into a three-dimensional network.
Methyl 2-amino-4,5-dimethoxybenzoate
Authors: Hill Tania N. , Patel Naadiya
Published: November 2013

The title compound, C10H13NO4, is essentially planar, with an r.m.s. deviation of 0.049 Å. An intramolecular C—H...O hydrogen bond occurs and the amino group forms an intramolecular N—H...Oesterhydrogen bond; the other H atom forms an intermolecular N—H...Ocarbonylhydrogen bond, leading to the formation of a helical chain that runs along theb-axis direction.
Bis(3-azaniumylpropyl)azanium hexachloridobismuthate(III) monohydrate
Authors: Elfaleh Nizar , Chouaib Hassen , Kamoun Slaheddine
Published: November 2013

The asymmetric unit of the title compound, (C6H20N3)[BiCl6]·H2O, consists of a triprotonated bis(3-azaniumylpropyl)azanium cation, two halves of an octahedral [BiCl6]3−anion, each of the BiIIIatoms lying on an inversion centre, and a water molecule. In the crystal, the anions and water molecules are linked by O—H...Cl hydrogen bonds, forming chains running parallel to [0-11]. The anionic chains and the cations are further linked into a three-dimensional network by N—H...Cl and N—H...O hydrogen-bond interactions.
The impact of genomic variability on gene expression in environmental Saccharomyces cerevisiae strains
Authors: Treu Laura , Toniolo Chiara , Nadai Chiara , Sardu Alessandro , Giacomini Alessio , Corich Viviana , Campanaro Stefano
Published: November 2013

Environmental Saccharomyces cerevisiae strains are crucially important, as they represent the large pool from which domesticated industrial yeasts have been selected, and vineyard strains can be considered the genetic reservoir from which industrial wine strains with strong fermentative behaviour are selected. Four vineyard strains with different fermentation performances were chosen from a large collection of strains isolated from Italian vineyards. Their genomes were sequenced to identify how genetic variations influence gene expression during fermentation and to clarify the evolutionary relationship between vineyard isolates and industrial wine strains. RNA sequencing was performed on the four vineyard strains, as well as on the industrial wine yeast strain EC1118 and on the laboratory strain S288c, at two stages of fermentation. We showed that there was a large gene cluster with variable promoter regions modifying gene expression in the strains. Our results indicate that it is the evolvability of the yeast promoter regions, rather than structural variations or strain‐specific genes, that is the main cause of the differences in gene expression. This promoter variability, determined by variable tandem repeats and a high number of single‐nucleotide polymorphisms together with 49 differentially expressed transcription factors, explained the strong phenotypic differences in the strains.
Anaerobic degradation of homocyclic aromatic compounds via arylcarboxyl‐coenzymeAesters: organisms, strategies and key enzymes
Authors: Boll Matthias , Löffler Claudia , Morris Brandon E. L. , Kung Johannes W.
Published: November 2013

Next to carbohydrates, aromatic compounds are the second most abundant class of natural organic molecules in living organic matter but also make up a significant proportion of fossil carbon sources. Only microorganisms are capable of fully mineralizing aromatic compounds. While aerobic microbes use well‐studied oxygenases for the activation and cleavage of aromatic rings, anaerobic bacteria follow completely different strategies to initiate catabolism. The key enzymes related to aromatic compound degradation in anaerobic bacteria are comprised of metal‐ and/or flavin‐containing cofactors, of which many use unprecedented radical mechanisms forC–Hbond cleavage or dearomatization. Over the past decade, the increasing number of completed genomes has helped to reveal a large variety of anaerobic degradation pathways inProteobacteria,Gram‐positive microbes and in one archaeon. This review aims to update our understanding of the occurrence of aromatic degradation capabilities in anaerobic microorganisms and serves to highlight characteristic enzymatic reactions involved in (i) the anoxic oxidation of alkyl side chains attached to aromatic rings, (ii) the carboxylation of aromatic rings and (iii) the reductive dearomatization of central arylcarboxyl‐coenzymeAintermediates. Depending on the redox potential of the electron acceptors used and the metabolic efficiency of the cell, different strategies may be employed for identical overall reactions.
Isolation of heterotrophic diazotrophic bacteria from estuarine surface waters
Authors: Farnelid Hanna , Harder Jens , Bentzon‐Tilia Mikkel , Riemann Lasse
Published: November 2013

The wide distribution of diverse nitrogenase (nifH) genes affiliated with those of heterotrophic bacteria in marine and estuarine waters indicates ubiquity and an ecologically relevant role for heterotrophic N2‐fixers (diazotrophs) in aquatic nitrogen (N) cycling. However, the lack of cultivated representatives currently precludes an evaluation of their N2‐fixing capacity. In this study, microoxic or anoxic N‐free media were inoculated with estuarine Baltic Sea surface water to select for N2‐fixers. After visible growth and isolation of single colonies on oxic plates or in anoxic agar tubes, nifH gene amplicons were obtained from 64 strains and nitrogenase activity, applying the acetylene reduction assay, was confirmed for 40 strains. Two strains, one Gammaproteobacterium affiliated with Pseudomonas and one Alphaproteobacterium affiliated with Rhodopseudomonas were shown to represent established members of the indigenous diazotrophic community in the Baltic Sea, with abundances of up to 7.9 × 104 and 4.7 × 104 nifH copies l−1 respectively. This study reports media for successful isolation of heterotrophic diazotrophs. The applied methodology and the obtained strains will facilitate future identification of factors controlling heterotrophic diazotrophic activity in aquatic environments, which is a prerequisite for understanding and evaluating their ecology and contribution to N cycling at local and regional scales.
Salivary cortisol levels, but not salivary α‐amylase levels, are elevated in patients with rheumatoid arthritis irrespective of depression
Authors: Kim Hyoun‐Ah , Jeon Ja‐Young , Koh Bo‐Ram , Park Sat‐Byul , Suh Chang‐Hee
Published: November 2013

Objectives

Stress is recognized as an important factor in the etiology of rheumatoid arthritis (RA). Therefore, we explored multiple aspects of stress in RA patients.

Methods

Salivary cortisol and α‐amylase levels were measured as markers of the hypothalamic–pituitary–adrenal axis activity and sympatho‐adrenomedullary system activity, respectively. Depression was assessed by the Beck Depression Inventory (BDI) and short‐term analysis of the heart rate variability (HRV) was performed to evaluate the autonomic nervous system.

Results

The salivary cortisol levels of the RA patients were significantly higher than those of the normal controls (NC; 0.12 ± 0.162 μg/dL vs. 0.068 ± 0.052 μg/dL, P = 0.006). There was no difference in salivary α‐amylase levels between the RA and the NC. The BDI levels of the RA patients were significantly higher than the NC (13.7 ± 8.9 vs. 6.4 ± 6.9, P < 0.001). Depression was more prevalent in RA patients than in the NC. The salivary cortisol levels were still significantly higher in the RA than the NC after controlling BDI by logistic regression analysis (P = 0.002). There was no significant difference in the HRV of RA patients and the NC. The evaluation of relationship between stress measures and disease activity markers of RA revealed that only BDI was positively correlated with the visual analogue pain scale.

Conclusion

Salivary cortisol levels and the BDI of RA patients were higher than those of the NC, and elevated salivary cortisol levels were independent of depression. However, the level of stress may not be correlated with disease activity in RA.
Methylation of a CpG Site Near the ALDH1A2 Gene is Associated with Loss of Control Over Drinking and Related Phenotypes
Authors: Harlaar Nicole , Bryan Angela D. , Thayer Rachel E. , Karoly Hollis C. , Oien Niles , Hutchison Kent E.
Published: November 2013

Background

The pathophysiology of alcohol use disorders (AUDs) may be influenced by epigenetics processes such as DNA methylation, but the identification of DNA methylation patterns associated with AUDs has largely been limited to a handful of candidate genes.

Methods

Participants were hazardous drinkers from the local community (n = 309). All participants completed a baseline clinical interview in which they reported on their loss of control over drinking. A subsample participated in an ethanol (EtOH) infusion experiment (n = 50). DNA was extracted from saliva samples and assayed on the Illumina Infinium HumanMethylation27 DNA Analysis BeadChip.

Results

We identified significant associations between loss of control over drinking and DNA methylation at multiple CpG sites. In follow‐up analyses of one of our top results, a CpG site near the ALDH1A2 gene, we found that methylation was negatively associated with rate of intoxication and self‐reported feelings of intoxication, consistent with the view that DNA methylation at ALDH1A2 may be associated with changes in alcohol metabolism.

Conclusions

While these findings require replication, they provide evidence that DNA methylation at multiple CpG sites is associated with loss of control over drinking. It may be useful to examine DNA methylation patterns using several related phenotypes to establish the biological coherence of results and to help prioritize markers for further study.
Population Pharmacokinetic–Pharmacogenetic Model of Tacrolimus in the Early Period after Kidney Transplantation
Authors: Han Nayoung , Ha Soojung , Yun Hwi‐yeol , Kim Myeong Gyu , Min Sang‐Il , Ha Jongwon , Lee Jangik Ike , Oh Jung Mi , Kim In‐Wha
Published: November 2013

As tacrolimus has a rather narrow therapeutic range and high individual variability in its pharmacokinetics, it is important to determine the cause of the variation in tacrolimus pharmacokinetics. The purpose of this study was to establish a population pharmacokinetic–pharmacogenetic model of tacrolimus and identify covariates that affect pharmacokinetic parameters to prevent fluctuations in the tacrolimus trough concentration during the early period after transplantation. Data from 1501 trough concentrations and 417 densely collected concentrations were compiled from 122 patients who were on post‐operative days 10–20 and analysed with a nonlinear mixed‐effect model. The first‐order conditional estimation (FOCE) with interaction method was used to fit the model using the NONMEM program. Clinical/laboratory data were also collected for the same period, and CYP3A5 and ABCB1 genotypes were analysed for use in modelling from all included patients. An empirical Bayesian approach was used to estimate individual pharmacokinetic profiles. A one‐compartment model with first absorption and elimination and lag time best described the data. The estimated population mean of clearance (CL/F), volume of distribution (V/F) and absorption rate (Ka) were 21.9 L/hr, 205 L, and 3.43/hr, respectively, and the lag time was fixed at 0.25 hr. Clearance increased with days after transplantation and decreased with CYP3A5*3/*3 about 18.4% compared with CYP3A5*1 carriers (p < 0.001). A population pharmacokinetic model was developed for tacrolimus in early post‐kidney transplantation recipients to identify covariates that affect tacrolimus pharmacokinetics. Post‐operative days and CYP3A5 genotype were confirmed as critical factors of tacrolimus pharmacokinetics.
Enhanced susceptibility of B lymphoma cells to measles virus by Epstein–Barr virus type III latency that upregulates CD150/signaling lymphocytic activation molecule
Authors: Takeda Satoshi , Kanbayashi Daiki , Kurata Takako , Yoshiyama Hironori , Komano Jun
Published: November 2013

Measles virus (MV) is one of the candidates for the application of oncolytic virotherapy (OVT). Although an advanced clinical study has been reported on a T‐cell lymphoma, the potential of MV OVT against B‐cell lymphomas remains to be clarified. We found that an EBV‐transformed B lymphoblastoid cell line, a model for diffuse large B‐cell lymphoma, and EBV‐positive Burkitt's lymphoma cells bearing type III latency were highly susceptible to the cytolysis induced by an MV vaccine strain CAM‐70. As analyzed by EBV‐positive and ‐negative counterparts of the same cytogenetic background, type III EBV latency, not type I, was shown to augment the susceptibility of B lymphoma cells to MV‐induced cytolysis. Cell surface levels of CD150/signaling lymphocytic activation molecule, a receptor of MV, were upregulated in B lymphoma cell lines with type III EBV latency by 3.8‐fold, on average. The cytolytic activity of CD150‐tropic WT MV was akin to that of CD46‐ and CD150‐tropic CAM‐70, suggesting that CD150 is critical for the susceptibility to MV‐induced cytolysis. Among EBV‐encoded genes, latent membrane protein 1 was responsible for the CD150 upregulation. It was notable that the majority of B lymphoma cell lines of type III EBV latency showed higher susceptibility to the non‐Edmonston‐derived CAM‐70 than to the Edmonston‐derived Schwarz strain. This is the first report indicating the potential of non‐Edmonston MV strain for the application of OVT. Furthermore, a cellular regulator of MV replication was implicated that functions in a vaccine strain‐specific fashion. Altogether, the MV OVT should serve as an alternative therapy against EBV‐positive diffuse large B‐cell lymphoma with type III EBV latency.
Pancreatic neuroendocrine tumour grading on endoscopic ultrasound‐guided fine needle aspiration: high reproducibility and inter‐observer agreement of the Ki‐67 labelling index
Authors: Weynand B. , Borbath I. , Bernard V. , Sempoux C. , Gigot J.‐F. , Hubert C. , Lannoy V. , Deprez P. H. , Jouret‐Mourin A.
Published: November 2013

Objectives

Assessment of proliferation by the Ki‐67 labelling index (Ki67‐LI) is an important parameter of pancreatic neuroendocrine tumour (pNET) prognosis on resection specimens. Ki67‐LI values for grading are not fully established on endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA). The aim of the study was to determine the accuracy of Ki67‐LI on EUS‐FNA to predict a final grade of pNET and to analyse the relationship between cytological grading and progression‐free survival (PFS).

Methods

Between 1996 and 2010, 46 pNETs (33 were resected) from 45 patients were diagnosed by EUS‐FNA. Ki67‐LI was evaluated on cytological and histological material for each tumour and classified according to the 2010 WHO grading system.

Results

A very good inter‐observer agreement for Ki67‐LI on EUS‐FNA and surgical specimens, respectively, were obtained. Discrepancies were observed between histology and cytology, especially in grade 2 (G2) tumours, where cytology underestimated grading owing to tumour heterogeneity. Still, EUS‐FNA was able to distinguish a poor prognostic group, as the actuarial PFS of cytological (c) G3 tumours was 10 ± 4 months versus 29 ± 7 and 68 ± 10 for cG2 and cG1 tumours, respectively (P < 0.0001).

Conclusion

This study attests the reproducibility of Ki67‐LI of pNETs whether counted on cytology or histology with a very good inter‐observer correlation. Determination of Ki67‐LI on EUS‐FNA of pNETs should be included systematically in their prognostic work‐up.
Accounting for false positives improves estimates of occupancy from key informant interviews
Authors: Pillay Rajeev , Miller David A. W. , Hines James E. , Joshi Atul A. , Madhusudan M. D.
Published: November 2013

Aim

Much research in conservation biogeography is fundamentally dependent on obtaining reliable data on species distributions across space and time. Such data are now increasingly being generated using various types of public surveys. These data are often integrated with occupancy models to evaluate distributional patterns, range dynamics and conservation status of multiple species at broad spatio‐temporal scales. Occupancy models have traditionally corrected for imperfect detection due to false negatives while implicitly assuming that false positives do not occur. However, public survey data are also prone to false‐positive errors, which when unaccounted for can cause bias in occupancy estimates. We test whether false positives in a dataset collected from public surveys lead to overestimation of species site occupancy and whether estimators that simultaneously account for false‐positive and false‐negative errors improve occupancy estimates.

Location

Western Ghats, India.

Methods

We fit occupancy models that simultaneously account for false positives and negatives to data collected from a large‐scale key informant interview survey for 30 species of large vertebrates. We tested their performance against standard occupancy models that account only for false negatives.

Results

Standard occupancy models that correct only for false negatives tended to overestimate species occupancy due to false‐positive errors. Occupancy models that simultaneously accounted for false positives and negatives had greater support [lower Akaike's information criterion (AIC)] and, consistent with predictions, generated systematically lower occupancy estimates than standard models. Furthermore, accounting for false positives improved the accuracy of occupancy estimates despite the added complexity to the statistical estimator.

Main conclusions

Integrating large‐scale public surveys with occupancy modelling approaches is a powerful tool for informing conservation and management. However, in many if not most cases, it will be important to explicitly account for false positives to ensure the reliability of occupancy estimates obtained from public survey datasets such as key informant interviews, volunteer surveys, citizen science programmes, historical archives and acoustic surveys.
Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon‐β therapy
Authors: Freedman M. S.
Published: November 2013

Background and purpose

Although the first‐line disease‐modifying therapies (DMTs) interferon beta and glatiramer acetate have a favourable benefit‐to‐risk profile, they are only partially effective for treating relapsing–remitting multiple sclerosis (RRMS). The optimization of treatment in patients who do not show a maximum response to first‐line therapy is critical for achieving the best long‐term outcomes. Treatment strategies for patients with a suboptimal response include switching to another first‐line DMT or a second‐line DMT. Natalizumab and fingolimod are approved for RRMS with high disease activity in the European Union and Canada.

Methods

A comprehensive literature search for articles published between 1990 and April 2012 was undertaken.

Results

This review discusses key clinical and safety data for fingolimod and natalizumab, particularly in the patient subgroups for whom these treatments are approved. Benefit‐to‐risk profiles, including first‐dose cardiovascular effects associated with fingolimod and the risk of progressive multifocal encephalopathy with natalizumab, are discussed.

Conclusion

A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision‐making process of how and when to switch patients who have a suboptimal response to first‐line therapy.
Effects of desiccation and rewetting on the release and decomposition of dissolved organic carbon from benthic macroalgae
Authors: Wyatt Kevin H. , Rober Allison R. , Schmidt Nicole , Davison Ian R.
Published: November 2013

Dissolved organic carbon (DOC) released by benthic algae is an important energy source in shallow aquatic ecosystems. Here, we evaluated the amount, composition and decomposition of DOC released by the benthic macroalga, Cladophora glomerata, during constant hydration and upon rewetting after drying for 0.5, 1, 2, 3 or 6 h on the shoreline of Lake Michigan, U.S.A.

Brief desiccation (0.5 h) significantly reduced gross primary productivity (mg C g dry mass−1 h−1) to 0.43 ± 0.13 from 5.66 ± 0.35 for continuously wet algae.

When continuously wet, Cladophora filaments released 1.71 ± 0.26 mg DOC g DM−1 h−1 into the surrounding water, representing 30% of carbon fixation; release increased to 7.64 ± 1.08 after 1 h and peaked at 12.18 ± 0.57 after 6 h of drying. Percent extracellular release exceeded carbon fixation upon rewetting after 0.5‐h desiccation and remained above 100% for each time interval thereafter.

The composition of exudates changed with time of desiccation. Carbohydrate release increased from 0.84 ± 0.13 to 3.0 ± 0.14 mg g DM−1 h−1 from 0 to 6 h desiccation, but declined as a percentage of total DOC from 49 to 25% over the same time. This reflected the much greater increase in protein yield from 0.40 ± 0.06 mg g DM−1 h−1 for wet algae to 7.70 ± 0.36 at 6‐h desiccation (24 and 63% of total DOC release, respectively). The proportion of carbohydrates to proteins decreased with desiccation time, from 2 : 1 at 0 h to 1 : 2.5 at 6 h.

Exudates from constantly hydrated algae (DOC0) and upon rewetting after 6‐h desiccation (DOC6) were degraded by more than 20% over 48 h of incubation inside dark bottles inoculated with the natural microbial community (10% lake water). Both treatments supported an exponential increase in bacterial density, but a greater proportion of DOC0 was used by bacteria after 12 days. Bacterial density increased from 0.09 ± 0.001 to 3.30 ± 0.11 106 cells mL−1 between 0‐ and 12‐day incubation in the DOC0 treatment and from 0.09 ± 0.008 to 2.64 ± 0.10 during the same time period in the DOC6 treatment.

Short‐term desiccation results in a substantial release of DOC from Cladophora that is used rapidly by bacteria in the overlying water column. The drying–rewetting cycle could be important for organic matter cycling in freshwater ecosystems where benthic macroalgae occur.
Information literacy: perceptions of Brazilian HIV/AIDS researchers
Authors: Alvarez Maria do Carmo Avamilano , França Ivan , Cuenca Angela Maria Belloni , Bastos Francisco I. , Ueno Helene Mariko , Barros Cláudia Renata , Guimarães Maria Cristina Soares
Published: November 2013

Background

Information literacy has evolved with changes in lifelong learning. Can Brazilian health researchers search for and use updated scientific information?

Objectives

To describe researchers' information literacy based on their perceptions of their abilities to search for and use scientific information and on their interactions with libraries.

Methods

Semi‐structured interviews and focus group conducted with six Brazilian HIV/AIDS researchers. Analyses comprised the assessment of researchers as disseminators, their interactions with librarians, their use of information and communication technology and language.

Results

Interviewees believed they were partially qualified to use databases. They used words and phrases that indicated their knowledge of technology and terminology. They acted as disseminators for students during information searches. Researchers' abilities to interact with librarians are key skills, especially in a renewed context where libraries have, to a large extent, changed from physical spaces to digital environments.

Discussion

Great amounts of information have been made available, and researchers' participation in courses does not automatically translate into adequate information literacy. Librarians must help research groups, and as such, librarians' information literacy‐related responsibilities in Brazil should be redefined and expanded.

Conclusions

Students must develop the ability to learn quickly, and librarians should help them in their efforts. Librarians and researchers can act as gatekeepers for research groups and as information coaches to improve others' search abilities.
The t(14;18)(q32;q21)/IGH–MALT1 translocation in gastrointestinal extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma)
Authors: Zhang Shimin , Wei Minqi , Liang Qi , Johnson Daisy , Dow Nancy , Nelson Ann , Aguilera Nadine , Auerbach Aaron , Wang Guanghua
Published: November 2013

Aims

Studies have indicated that the t(14;18)(q32;q21)/IGH–MALT1 translocation is present in extranodal marginal zone lymphomas of mucosa‐associated lymphoid tissue (MALT lymphoma). However, only a few studies have investigated the incidence of t(14;18)/IGH–MALT1 in primary gastrointestinal MALT lymphomas or in diffuse large B‐cell lymphomas (DLBCL). The overall significance of t(14;18)/IGH–MALT1 in gastrointestinal MALT lymphomas is not clear. We examined 41 gastrointestinal MALT lymphoma and 23 DLBCL cases, with the aim of further understanding the role of t(14;18)/IGH–MALT1 in these diseases.

Methods and results

Fluorescence in‐situ hybridization (FISH) assays for the detection of t(14;18)/IGH–MALT1 and t(11;18)(q21;q21)/API2–MALT1, along with immunostaining and histological evaluations, were performed on selected cases. Of the 64 analysed cases, one gastric MALT lymphoma and one colonic MALT lymphoma were positive for t(14;18)/IGH–MALT1.

Conclusions

We describe what are, to our knowledge, the first reported primary colonic MALT lymphoma carrying t(14;18)(q32;q21)/IGH–MALT1, and one of the few reported cases of gastric MALT lymphoma with this translocation. As this translocation is seen in only a few gastrointestinal MALT lymphomas, it is not useful as a diagnostic marker for routine clinical services. Although these findings suggest that t(14;18)/IGH–MALT1 is a rare molecular event in gastrointestinal MALT lymphomas and DLBCLs, further studies to elucidate the role of this genetic alteration in these diseases are indicated.
DOGS, HISTORY, AND AGENCY
Authors: PEARSON CHRIS
Published: November 2013

Drawing on posthumanist theories from geography, anthropology, and science and technology studies (STS), this article argues that agency is shared unevenly between humans and nonhumans. It proposes that conceptualizing animals as agents allows them to enter history as active beings rather than static objects. Agency has become a key concept within history, especially since the rise of the “new” social history. But many historians treat agency as a uniquely human attribute, arguing that animals lack the cognitive abilities, self‐awareness, and intentionality to be agents. This article argues that human levels of intentionality are not a precondition of agency. Furthermore, it draws on research into canine psychology to propose that dogs display some degree of intentionality and self‐directed action. The aim is not to turn dogs, or any other animals, into human‐style agents nor to suggest that they display the same levels of skill, intentionality, and intelligence as humans. Instead, the objective is to show how dogs are purposeful and capable agents in their own way and to explore how they interact with human agents. The article particularly considers the agency of militarized dogs, especially those on the Western Front (1914–1918), to suggest how historians can use primary sources to uncover how individuals in the past have treated dogs as capable creatures and to capture some sense of dogs’embodied and purposeful agency.
Basal expression of growth‐factor‐associated genes in periodontal ligament stem cells reveals multiple distinctive pathways
Authors: Osman A. , Gnanasegaran N. , Govindasamy V. , Kathivaloo P. , Wen A. S. , Musa S. , Abu Kasim N. H.
Published: November 2013

Aim

To identify and compare the expression level of growth‐factor‐associated genes in human periodontal ligament (PDL) stem cells with dental pulp stem cells isolated from deciduous teeth as well as to assess their suitability in regenerative dentistry.

Methodology

Periodontal ligament and dental pulp stem cells were isolated from deciduous teeth. Human both cells lines were expanded in identical culture condition, and their differentiation profile and cell surface antigen were compared. In addition, growth factor associated genes profiles were assessed using PCR array.

Results

Stem cells from deciduous dental pulp (SCD) and periodontal ligament cultures were capable of proliferating and mutually expressed the specific phenotype profile of human mesenchymal stem cells (MSCs). In osteogenic cultures, calcium nodules were observed by day 21 in PDL and dental pulp stem cells. In adipogenic cultures, both cell populations showed positive Oil Red O staining by day 21. Likewise, in chondrogenic cultures, both stem cells expressed the formation of proteoglycan. Interestingly, the expression of growth factor analysis revealed a higher propensity of PDL stem cells towards angiogenesis, osteogenesis and neurogenesis as compared to dental pulp stem cells.

Conclusions

The data suggest the PDL stem cell population can be utilized as potential sources for cell‐based therapies in regenerative dentistry.
The evolving role of nurses in primary care medical settings
Authors: Oelke Nelly D , Besner Jeanne , Carter Rebecca
Published: November 2013

The role of nurses in primary care is understudied. The purpose of this study was to describe the current registered nurse (RN) role in three Primary Care Networks (PCNs) in western Canada and to identify opportunities for optimal utilization of RNs in these settings. Case study methodology included interviews and document review. Although the RN role evolved during the study, most RNs focused on chronic disease management. Role ambiguity was evident between nurses and with interprofessional team members. Relationships of RNs to other providers, particularly physicians, impacted the enactment of the nursing role. Other barriers to role enactment included physician fee‐for‐service remuneration, management structures and processes, lack of access to electronic medical records and lack of previous opportunities to apply primary health‐care education in the practice setting. Further work is needed to optimize the RN role in primary care to ensure maximum impact for patients, providers and the health system overall.
MicroRNA levels are modulated in Aedes aegypti after exposure to Dengue‐2
Authors: Campbell C. L. , Harrison T. , Hess A. M. , Ebel G. D.
Published: November 2013

To define microRNA (miRNA) involvement during arbovirus infection of Aedes aegypti, we mined deep sequencing libraries of Dengue type 2 (DENV2)‐exposed mosquitoes. Three biological replicates for each timepoint [2, 4 and 9 days post‐exposure (dpe)] and treatment group allowed us to remove the outliers associated with sample‐to‐sample variability. Using edgeR (R Bioconductor), designed for use with replicate deep sequencing data, we determined the log fold‐change (logFC) of miRNA levels [18–23 nucleotides (nt)]. The number of significantly modulated miRNAs increased from ≤5 at 2 and 4 dpe to 23 unique miRNAs by 9 dpe. Putative miRNA targets were predicted by aligning miRNAs to the transcriptome, and the list was reduced to include the intersection of hits found using the Miranda, PITA, and TargetScan algorithms. To further reduce false‐positives, putative targets were validated by cross‐checking them with mRNAs reported in recent DENV2 host response transcriptome reports; 4076 targets were identified. Of these, 464 gene targets have predicted miRNA‐binding sites in 3′ untranslated regions. Context‐specific target functional groups include proteins involved in transport, transcriptional regulation, mitochondrial function, chromatin modification and signal transduction processes known to be required for viral replication and dissemination. The miRNA response is placed in context with other vector host response studies by comparing the predicted targets with those of transcriptome studies. Together, these data are consistent with the hypothesis that profound and persistent changes to gene expression occur in DENV2‐exposed mosquitoes.
Attitudes towards female genital mutilation: an integrative review
Authors: Reig Alcaraz M. , Siles González J. , Solano Ruiz C.
Published: November 2013

Background

Immigration and globalization processes have contributed to the international dissemination of practices such as female genital mutilation. Between 100 and 400 million girls and women have been genitally mutilated, and every year 3 million girls are at risk of being subjected to female genital mutilation.

Objectives

The objective of this study was to describe the attitudes towards the practice of female genital mutilation in relation to different health systems and the factors that favour its discontinuation.

Methods

An integrative review was performed of publications from the period 2006 to 2013 included in the MedLine, PubMed, LILACS, SciELO, CINAHL and CUIDEN databases.

Results

We selected 16 studies focusing on diverse contexts that assessed the attitudes of both men and women regarding the perpetuation of this practice. Ten corresponded to studies conducted in countries of residence. Several areas of investigation were explored (factors contributing to the continuation of female genital mutilation, factors contributing to its discontinuation, feelings about the health system).

Limitations

It is possible that the relevant studies may not have been included given the limitations of the literature review and the invisibility of the phenomenon studied.

Conclusions

This review demonstrates the strong social pressure to which women are subjected as regards the practice of female genital mutilation. However, many other factors can contribute to eroding beliefs and arguments in favour of this practice, such as the globalization, culture and social environment of countries in the West.

Implications for nursing and health policy

Nurses occupy an essential position in detecting and combating these practices.
Doppler optical coherence tomography
Authors: SCHMETTERER L
Published: November 2013

Doppler optical coherence tomography (OCT) is a functional extension of OCT. In Fourier Domain OCT information on blood flow can be extracted when phase‐sensitive measurements are performed. This technique can be used to quantify blood flow but also to visualize the vasculature comparable to angiography. When blood flow in the retina is quantified knowledge on the orientation of the vessel relative to the illuminating laser beam is required. Several attempts have been tried to solve this problem. A promising technique is to illuminate the vessel from two directions with two laser beams. With this approach the extraction of blood velocity becomes independent of incident angle and independent of eye movements. We have shown that this is a vlid and reproducible technique to quantify retinal blood flow in humans. When doing angiography systems with high readout rate are required, because of motion artifacts. The technique may have significant potential in retinal disease.
Prognostic factors for clinical outcomes in patients with Vogt‐Koyanagi‐Harada disease treated with high‐dose corticosteroids
Authors: ABU EL ASRAR A
Published: November 2013

Purpose: To determine prognostic factors in patients with Vogt‐Koyanagi‐Harada (VKH) disease who were treated with high‐dose corticosteroids. Methods: Analysis of 87 patients (174 eyes). Results: Chronic recurrent presentation was significantly associated with more severe anterior segment inflammation at presentation as indicated by presence of mutton‐fat keratic precipitates, anterior chamber reaction of 2+ or more, iris nodules and posterior synechiae, less exudative retinal detachment at presentation, more complications during the follow‐up period and a worse visual outcome. The use of immunomodulatory therapy as first line therapy significantly reduced the development of complications in the whole study group and in initial‐onset acute group and improved visual outcome in the whole study group. In the whole study group, final visual acuity of 20/20 was significantly associated with good initial visual acuity of >20/200 and age older than 16 years was significantly associated with the development of complications. Conclusions: Chronic recurrent VKH disease is significantly associated with more severe inflammation at presentation and more complications. Use of immunomodulatory therapy improves clinical outcome.