bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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.
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

SummaryEnvironmental 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

SummaryNext 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

SummaryThe 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

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

BackgroundThe 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.MethodsParticipants 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.ResultsWe 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.ConclusionsWhile 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

AbstractAs 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.
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

ObjectivesAssessment 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).MethodsBetween 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.ResultsA 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).ConclusionThis 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

AbstractAimMuch 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.LocationWestern Ghats, India.MethodsWe 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.ResultsStandard 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 conclusionsIntegrating 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 purposeAlthough 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.MethodsA comprehensive literature search for articles published between 1990 and April 2012 was undertaken.ResultsThis 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.ConclusionA 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

Summary

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

AbstractBackgroundInformation literacy has evolved with changes in lifelong learning. Can Brazilian health researchers search for and use updated scientific information?ObjectivesTo describe researchers' information literacy based on their perceptions of their abilities to search for and use scientific information and on their interactions with libraries.MethodsSemi‐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.ResultsInterviewees 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.DiscussionGreat 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.ConclusionsStudents 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.