bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide linkage analyses identify Hfhl1 and Hfhl3 with frequency-specific effects on the hearing spectrum of NIH Swiss mice
Authors: Keller James M , Noben-Trauth Konrad
Published: April 2012

Background

The mammalian cochlea receives and analyzes sound at specific places along the cochlea coil, commonly referred to as the tonotopic map. Although much is known about the cell-level molecular defects responsible for severe hearing loss, the genetics responsible for less severe and frequency-specific hearing loss remains unclear. We recently identified quantitative trait loci (QTLs) Hfhl1 and Hfhl2 that affect high-frequency hearing loss in NIH Swiss mice. Here we used 2f1-f2 distortion product otoacoustic emissions (DPOAE) measurements to refine the hearing loss phenotype. We crossed the high frequency hearing loss (HFHL) line of NIH Swiss mice to three different inbred strains and performed linkage analysis on the DPOAE data obtained from the second-generation populations.

Results

We identified a QTL of moderate effect on chromosome 7 that affected 2f1-f2 emissions intensities (Hfhl1), confirming the results of our previous study that used auditory brainstem response (ABR) thresholds to identify QTLs affecting HFHL. We also identified a novel significant QTL on chromosome 9 (Hfhl3) with moderate effects on 2f1-f2 emissions intensities. By partitioning the DPOAE data into frequency subsets, we determined that Hfhl1 and Hfhl3 affect hearing primarily at frequencies above 24 kHz and 35 kHz, respectively. Furthermore, we uncovered additional QTLs with small effects on isolated portions of the DPOAE spectrum.

Conclusions

This study identifies QTLs with effects that are isolated to limited portions of the frequency map. Our results support the hypothesis that frequency-specific hearing loss results from variation in gene activity along the cochlear partition and suggest a strategy for creating a map of cochlear genes that influence differences in hearing sensitivity and/or vulnerability in restricted portions of the cochlea.
Genetic characterization of Plectorhinchus mediterraneus yields important clues about genome organization and evolution of multigene families
Authors: Merlo Manuel A , Pacchiarini Tiziana , Portela-Bens Silvia , Cross Ismael , Manchado Manuel , Rebordinos Laureana
Published: April 2012

Background

Molecular and cytogenetic markers are of great use for to fish characterization, identification, phylogenetics and evolution. Multigene families have proven to be good markers for a better understanding of the variability, organization and evolution of fish species. Three different tandemly-repeated gene families (45S rDNA, 5S rDNA and U2 snDNA) have been studied inPlectorhinchus mediterraneus(Teleostei: Haemulidae), at both molecular and cytogenetic level, to elucidate the taxonomy and evolution of these multigene families, as well as for comparative purposes with other species of the family.

Results

Four different types of 5S rDNA were obtained; two of them showed a high homology with that ofRaja asterias, and the putative implication of a horizontal transfer event and its consequences for the organization and evolution of the 5S rDNA have been discussed. The other two types do not resemble any other species, but in one of them a putative tRNA-derived SINE was observed for the first time, which could have implications in the evolution of the 5S rDNA. The ITS-1 sequence was more related to a species of another different genus than to that of the same genus, therefore a revision of the Hamulidae family systematic has been proposed. In the analysis of the U2 snDNA, we were able to corroborate that U2 snDNA and U5 snDNA were linked in the same tandem array, and this has interest for tracing evolutionary lines. The karyotype of the species was composed of 2n = 48 acrocentric chromosomes, and each of the three multigene families were located in different chromosome pairs, thus providing three different chromosomal markers.

Conclusions

Novel data can be extracted from the results: a putative event of horizontal transfer, a possible tRNA-derived SINE linked to one of the four 5S rDNA types characterized, and a linkage between U2 and U5 snDNA. In addition, a revision of the taxonomy of the Haemulidae family has been suggested, and three cytogenetic markers have been obtained. Some of these results have not been described before in any other fish species. New clues about the genome organization and evolution of the multigene families are offered in this study.
Characterization of host microRNAs that respond to DNA virus infection in a crustacean
Authors: Huang Tianzhi , Xu Dandan , Zhang Xiaobo
Published: April 2012

Background

MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression that are implicated in many processes of eukaryotic cells. It is known that the expression profiles of host miRNAs can be reshaped by viruses. However, a systematic investigation of marine invertebrate miRNAs that respond to virus infection has not yet been performed.

Results

In this study, the shrimp Marsupenaeus japonicus was challenged by white spot syndrome virus (WSSV). Small RNA sequencing of WSSV-infected shrimp at different time post-infection (0, 6, 24 and 48 h) identified 63 host miRNAs, 48 of which were conserved in other animals, representing 43 distinct families. Of the identified host miRNAs, 31 were differentially expressed in response to virus infection, of which 25 were up-regulated and six down-regulated. The results were confirmed by northern blots. The TargetScan and miRanda algorithms showed that most target genes of the differentially expressed miRNAs were related to immune responses. Gene ontology analysis revealed that immune signaling pathways were mediated by these miRNAs. Evolutionary analysis showed that three of them, miR-1, miR-7 and miR-34, are highly conserved in shrimp, fruit fly and humans and function in the similar pathways.

Conclusions

Our study provides the first large-scale characterization of marine invertebrate miRNAs that respond to virus infection. This will help to reveal the molecular events involved in virus-host interactions mediated by miRNAs and their evolution in animals.
Hypochlorous acid and hydrogen peroxide-induced negative regulation of Salmonella enterica serovar Typhimurium ompW by the response regulator ArcA
Authors: Morales Eduardo H , Calderón Iván L , Collao Bernardo , Gil Fernando , Porwollik Steffen , McClelland Michael , Saavedra Claudia P
Published: April 2012

Background

Hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) are reactive oxygen species that are part of the oxidative burst encountered by Salmonella enterica serovar Typhimurium (S. Typhimurium) upon internalization by phagocytic cells. In order to survive, bacteria must sense these signals and modulate gene expression. Growing evidence indicates that the ArcAB two component system plays a role in the resistance to reactive oxygen species. We investigated the influx of H2O2 and HOCl through OmpW and the role of ArcAB in modulating its expression after exposure to both toxic compounds in S. Typhimurium.

Results

H2O2 and HOCl influx was determined both in vitro and in vivo. A S. Typhimurium ompW mutant strain (∆ompW) exposed to sub-lethal levels of H2O2 and HOCl showed a decreased influx of both compounds as compared to a wild type strain. Further evidence of H2O2 and HOCl diffusion through OmpW was obtained by using reconstituted proteoliposomes. We hypothesized that ompW expression should be negatively regulated upon exposure to H2O2 and HOCl to better exclude these compounds from the cell. As expected, qRT-PCR showed a negative regulation in a wild type strain treated with sub-lethal concentrations of these compounds. A bioinformatic analysis in search for potential negative regulators predicted the presence of three ArcA binding sites at the ompW promoter region. By electrophoretic mobility shift assay (EMSA) and using transcriptional fusions we demonstrated an interaction between ArcA and one site at the ompW promoter region. Moreover, qRT-PCR showed that the negative regulation observed in the wild type strain was lost in an arcA and in arcB mutant strains.

Conclusions

OmpW allows the influx of H2O2 and HOCl and is negatively regulated by ArcA by direct interaction with the ompW promoter region upon exposure to both toxic compounds.
Genome-wide association mapping of flowering time and northern corn leaf blight (Setosphaeria turcica) resistance in a vast commercial maize germplasm set
Authors: Van Inghelandt Delphine , Melchinger Albrecht E , Martinant Jean-Pierre , Stich Benjamin
Published: April 2012

Background

Setosphaeria turcicais a fungal pathogen that causes northern corn leaf blight (NCLB) which is a serious foliar disease in maize. In order to unravel the genetic architecture of the resistance against this disease, a vast association mapping panel comprising 1487 European maize inbred lines was used to (i) identify chromosomal regions affecting flowering time (FT) and northern corn leaf blight (NCLB) resistance, (ii) examine the epistatic interactions of the identified chromosomal regions with the genetic background on an individual molecular marker basis, and (iii) dissect the correlation between NCLB resistance and FT.

Results

The single marker analyses performed for 8 244 single nucleotide polymorphism (SNP) markers revealed seven, four, and four SNP markers significantly (α=0.05, amplicon wise Bonferroni correction) associated with FT, NCLB, and NCLB resistance corrected for FT, respectively. These markers explained individually between 0.36 and 14.29% of the genetic variance of the corresponding trait.

Conclusions

The very well interpretable pattern of SNP associations observed for FT suggested that data from applied plant breeding programs can be used to dissect polygenic traits. This in turn indicates that the associations identified for NCLB resistance might be successfully used in marker-assisted selection programs. Furthermore, the associated genes are also of interest for further research concerning the mechanism of resistance to NCLB and plant diseases in general, because some of the associated genes have not been mentioned in this context so far.
Including mixed methods research in systematic reviews: Examples from qualitative syntheses in TB and malaria control
Authors: Atkins Salla , Launiala Annika , Kagaha Alexander , Smith Helen
Published: April 2012

Background

Health policy makers now have access to a greater number and variety of systematic reviews to inform different stages in the policy making process, including reviews of qualitative research. The inclusion of mixed methods studies in systematic reviews is increasing, but these studies pose particular challenges to methods of review. This article examines the quality of the reporting of mixed methods and qualitative-only studies.

Methods

We used two completed systematic reviews to generate a sample of qualitative studies and mixed method studies in order to make an assessment of how the quality of reporting and rigor of qualitative-only studies compares with that of mixed-methods studies.

Results

Overall, the reporting of qualitative studies in our sample was consistently better when compared with the reporting of mixed methods studies. We found that mixed methods studies are less likely to provide a description of the research conduct or qualitative data analysis procedures and less likely to be judged credible or provide rich data and thick description compared with standalone qualitative studies. Our time-related analysis shows that for both types of study, papers published since 2003 are more likely to report on the study context, describe analysis procedures, and be judged credible and provide rich data. However, the reporting of other aspects of research conduct (i.e. descriptions of the research question, the sampling strategy, and data collection methods) in mixed methods studies does not appear to have improved over time.

Conclusions

Mixed methods research makes an important contribution to health research in general, and could make a more substantial contribution to systematic reviews. Through our careful analysis of the quality of reporting of mixed methods and qualitative-only research, we have identified areas that deserve more attention in the conduct and reporting of mixed methods research.
Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat
Authors: Koppelmann Tal , Pollak Yulia , Mogilner Jorge , Bejar Jacob , Coran Arnold G , Sukhotnik Igor
Published: April 2012

Background

Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat.

Methods

Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression.

Results

MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels.

Conclusions

Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.
Whole cell biosynthesis of a functional oligosaccharide, 2′-fucosyllactose, using engineered Escherichia coli
Authors: Lee Won-Heong , Pathanibul Panchalee , Quarterman Josh , Jo Jung-Hyun , Han Nam Soo , Miller Michael J , Jin Yong-Su , Seo Jin-Ho
Published: April 2012

Background

2'-Fucosyllactose (2-FL) is a functional oligosaccharide present in human milk which protects against the infection of enteric pathogens. Because 2-FL can be synthesized through the enzymatic fucosylation of lactose with guanosine 5′-diphosphate (GDP)-l-fucose by α-1,2-fucosyltransferase (FucT2), an 2-FL producing Escherichia coli can be constructed through overexpressing genes coding for endogenous GDP- l-fucose biosynthetic enzymes and heterologous fucosyltransferase.

Results

The gene for FucT2 from Helicobacter pylori was introduced to the GDP- l-fucose producing recombinant E. coli BL21 star(DE3) strain. However, only small amount of 2-FL was produced in a batch fermentation because the E. coli BL21star(DE3) strain assimilated lactose instead of converting to 2-FL. As an alternative host, the E. coli JM109(DE3) strain which is incapable of assimilating lactose was chosen as a 2-FL producer. Whole cell biosynthesis of 2-FL from lactose was investigated in a series of batch fermentations using various concentrations of lactose. The results of batch fermentations showed that lactose was slowly assimilated by the engineered E. coli JM109(DE3) strain and 2-FL was synthesized without supplementation of another auxiliary sugar for cell growth. A maximum 2-FL concentration of 1.23 g/l was obtained from a batch fermentation with 14.5 g/l lactose. The experimentally obtained yield (g 2-FL/g lactose) corresponded to 20% of the theoretical maximum yield estimated by the elementary flux mode (EFM) analysis.

Conclusions

The experimental 2-FL yield in this study corresponded to about 20% of the theoretical maximum yield, which suggests further modifications via metabolic engineering of a host strain or optimization of fermentation processes might be carried out for improving 2-FL yield. Improvement of microbial production of 2-FL from lactose by engineered E. coli would increase the feasibility of utilizing 2-FL as a prebiotic in various foods.
A rapid low-cost real-time PCR for the detection of klebsiella pneumonia carbapenemase genes
Authors: Wang Lijun , Gu Haitong , Lu Xinxin
Published: April 2012

Background

Klebsiella pneumonia carbapenemases (KPCs) are able to hydrolyze the carbapenems, which cause many bacteria resistance to multiple classes of antibiotics, so the rapid dissemination of KPCs is worrisome. Laboratory identification of KPCs-harboring clinical isolates would be a key to limit the spread of the bacteria. This study would evaluate a rapid low-cost real-time PCR assay to detect KPCs.

Methods

Real-time PCR assay based on SYBR GreenIwas designed to amplify a 106 bp product of the bla
KPC gene from the159 clinical Gram-negative isolates resistant to several classes of β-lactam antibiotics through antimicrobial susceptibility testing. We confirmed the results of real-time PCR assay by the conventional PCR-sequencing. At the same time, KPCs of these clinical isolates were detected by the modified Hodge test (MHT). Then we compared the results of real-time PCR assay with those of MHT from the sensitivity and specificity. Moreover, we evaluated the sensitivity of the real-time PCR assay.

Results

The sensitivity and specificity of the results of the real-time PCR assay compared with those of MHT was 29/29(100 %) and 130/130(100 %), respectively. The results of the real-time PCR and the MHT were strongly consistent (Exact Sig. (2-tailed) =1. 000; McNemar test). The real-time PCR detection limit was about 0.8 cfu using clinical isolates.

Conclusion

The real-time PCR assay could rapidly and accurately detect KPCs -harboring strains with high analytical sensitivity and specificity.
A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats
Authors: Aroor Annayya R , Roy Lowery J , Restrepo Ricardo J , Mooney Brian P , Shukla Shivendra D
Published: April 2012

Background

Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol- binge were compared.

Results

The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-binge. Ethanol binge alone in control rats had no effect on this protein suggesting its possible role in increased susceptibility to injury by binge after chonic ethanol treatment. A protein spot, in which both cytosolic isocitrate dehydrogenase (IDH1) and glutamine synthetase (GS) were identified, showed a small decrease after chronic ethanol binge but western blot demonstrated significant decrease only for glutamine synthetase in chronic ethanol treated rats. The level of gluathione S-transferase mu isoform (GSTM1) increased after chronic ethanol but was lower after chronic ethanol-binge compared to chronic ethanol treatment. The protein levels of the basic form of protein disulfide isomerase associated protein 3 (PDIA3) were significantly decreased and the acidic forms were increased after chronic ethanol- binge but not in chronic ethanol treated rats or ethanol binge in control rats. The significant changes in proteome profile in chronic ethanol binge were accompanied by a marked increase in liver injury as evidenced by enhanced steatosis, necrosis, increased 4-hydroxynonenal labeled proteins, CYP2E1 expression, and decreased histone H2AX phosphorylation.

Conclusions

Given the role of CA3, IDH1 and GST in oxidative stress; PDIA3 in protein quality control, apoptosis and DNA repair and decreased glutamine synthetase as a sensitive marker of pericentral liver injury this proteome study of chronic ethanol-binge rat model identifies these proteins for the first time as molecular targets with potential role in progression of liver injury by binge ethanol drinking.
Strong convergence theorems of nonlinear operator equations for countable family of multi-valued total quasi-ϕ-asymptotically nonexpansive mappings with applications
Authors: Chang Shih-Sen , Wang Lin , Tang Yong-Kun , Zhao Yun-He , Ma Zao-Li
Published: April 2012

The purpose of this article is first to introduce the concept of total quasi-ϕ-asymptotically nonexpansive multi-valued mapping which contains many kinds of mappings as its special cases, and then by using the hybrid shrinking technique to propose an iterative algorithm for finding a common element of the set of solutions for a generalized mixed equilibrium problem, the set of solutions for variational inequality problems, and the set of common fixed points for a countable family of multi-valued total quasi-ϕ-asymptotically nonexpansive mappings in a real uniformly smooth and strictly convex Banach space with Kadec-Klee property. The results presented in the article not only generalize some recent results from single-valued mappings to multi-valued mappings, but also improve and extend the main results of Homaeipour and Razani.

2000 AMS Subject Classification: 47J06; 47J25.
Pancreatogastrostomy versus pancreatojejunostomy for RECOnstruction after partial PANCreatoduodenectomy (RECOPANC): study protocol of a randomized controlled trial UTN U1111-1117-9588
Authors: Wellner Ulrich Friedrich , Brett Sabine , Bruckner Thomas , Limprecht Ronald , Rossion Inga , Seiler Christoph , Sick Olivia , Wegener Inga , Hopt Ulrich Theodor , Keck Tobias ,   RECOPANC Trial Group
Published: April 2012

Background

Pancreatoduodenectomy is one of the most complex abdominal operations, usually performed for tumors of the periampullary region and chronic pancreatitis. Leakage of pancreatic juice from the pancreatoenteric anastomosis, called postoperative pancreatic fistula, is the most prominent postoperative complication. Retrospective studies show a significant reduction of fistula rates with pancreatogastrostomy as compared to pancreatojejunostomy, the most frequently employed method of pancreatoenterostomy. Most single-center prospective trials, however, have not validated this finding. A large multicenter trial is needed for clarification.

Methods/design

RECOPANC is a prospective, randomized, controlled multicenter trial with two treatment arms, pancreatogastrostomy versus pancreatojejunostomy. The trial hypothesis is that postoperative pancreatic fistula rate is lower after pancreatogastrostomy when compared to pancreatojejunostomy. Fourteen academic centers for pancreatic surgery will participate to allocate 360 patients to the trial. The duration of the entire trial is four years including prearrangement and analyses.

Discussion

Postoperative pancreatic fistula is the main reason for clinically important postoperative morbidity after pancreatoduodenectomy. The primary goal of the chosen reconstruction technique for pancreatoenteric anastomosis is to minimize postoperative fistula rate. A randomized trial performed at multiple high-volume centers for pancreatic surgery is the best opportunity to investigate one of the most crucial issues in pancreatic surgery.

Trial registration

German Clinical Trials Register DRKS00000767 (2011/03/23), FSI 2011/05/31. Universal Trial Number U1111-1117-9588.
Assessment of behavioral changes associated with oral meloxicam administration at time of dehorning in calves using a remote triangulation device and accelerometers
Authors: Theurer Miles E , White Brad J , Coetzee Johann F , Edwards Lily N , Mosher Ruby A , Cull Charley A
Published: April 2012

Background

Dehorning is common in the cattle industry, and there is a need for research evaluating pain mitigation techniques. The objective of this study was to determine the effects of oral meloxicam, a non-steroidal anti-inflammatory, on cattle behavior post-dehorning by monitoring the percent of time spent standing, walking, and lying in specific locations within the pen using accelerometers and a remote triangulation device. Twelve calves approximately ten weeks of age were randomized into 2 treatment groups (meloxicam or control) in a complete block design by body weight. Six calves were orally administered 0.5 mg/kg meloxicam at the time of dehorning and six calves served as negative controls. All calves were dehorned using thermocautery and behavior of each calf was continuously monitored for 7 days after dehorning using accelerometers and a remote triangulation device. Accelerometers monitored lying behavior and the remote triangulation device was used to monitor each calf’s movement within the pen.

Results

Analysis of behavioral data revealed significant interactions between treatment (meloxicam vs. control) and the number of days post dehorning. Calves that received meloxicam spent more time at the grain bunk on trial days 2 and 6 post-dehorning; spent more time lying down on days 1, 2, 3, and 4; and less time at the hay feeder on days 0 and 1 compared to the control group. Meloxicam calves tended to walk more at the beginning and end of the trial compared to the control group. By day 5, the meloxicam and control group exhibited similar behaviors.

Conclusions

The noted behavioral changes provide evidence of differences associated with meloxicam administration. More studies need to be performed to evaluate the relationship of behavior monitoring and post-operative pain. To our knowledge this is the first published report demonstrating behavioral changes following dehorning using a remote triangulation device in conjunction with accelerometers.
Optimization of the examination posture in spinal curvature assessment
Authors: Krejci Jakub , Gallo Jiri , Stepanik Petr , Salinger Jiri
Published: April 2012

To decrease the influence of postural sway during spinal measurements, an instrumented fixation posture (called G) was proposed and tested in comparison with the free standing posture (A) using the DTP-3 system in a group of 70 healthy volunteers. The measurement was performed 5 times on each subject and each position was tested by a newly developed device for non-invasive spinal measurements called DTP-3 system. Changes in postural stability of the spinous processes for each subject/the whole group were evaluated by employing standard statistical tools. Posture G, when compared to posture A, reduced postural sway significantly in all spinous processes from C3 to L5 in both the mediolateral and anterioposterior directions. Posture G also significantly reduced postural sway in the vertical direction in 18 out of 22 spinous processes. Importantly, posture G did not significantly influence the spinal curvature.
Topological analysis of protein co-abundance networks identifies novel host targets important for HCV infection and pathogenesis
Authors: McDermott Jason E , Diamond Deborah L , Corley Courtney , Rasmussen Angela L , Katze Michael G , Waters Katrina M
Published: April 2012

Background

High-throughput methods for obtaining global measurements of transcript and protein levels in biological samples has provided a large amount of data for identification of 'target' genes and proteins of interest. These targets may be mediators of functional processes involved in disease and therefore represent key points of control for viruses and bacterial pathogens. Genes and proteins that are the most highly differentially regulated are generally considered to be the most important. We present topological analysis of co-abundance networks as an alternative to differential regulation for confident identification of target proteins from two related global proteomics studies of hepatitis C virus (HCV) infection.

Results

We analyzed global proteomics data sets from a cell culture study of HCV infection and from a clinical study of liver biopsies from HCV-positive patients. Using lists of proteins known to be interaction partners with pathogen proteins we show that the most differentially regulated proteins in both data sets are indeed enriched in pathogen interactors. We then use these data sets to generate co-abundance networks that link proteins based on similar abundance patterns in time or across patients. Analysis of these co-abundance networks using a variety of network topology measures revealed that both degree and betweenness could be used to identify pathogen interactors with better accuracy than differential regulation alone, though betweenness provides the best discrimination. We found that though overall differential regulation was not correlated between the cell culture and liver biopsy data, network topology was conserved to an extent. Finally, we identified a set of proteins that has high betweenness topology in both networks including a protein that we have recently shown to be essential for HCV replication in cell culture.

Conclusions

The results presented show that the network topology of protein co-abundance networks can be used to identify proteins important for viral replication. These proteins represent targets for further experimental investigation that will provide biological insight and potentially could be exploited for novel therapeutic approaches to combat HCV infection.
Haemophilus pittmaniae respiratory infection in a patient with siderosis: a case report
Authors: Boucher Mathilde Bouc , Bedotto Marielle , Couderc Carine , Gomez Carine , Reynaud-Gaubert Martine , Drancourt Michel
Published: April 2012

Introduction

Haemophilus pittmaniae was described in 2005 as a new species distantly related to Haemophilus parainfluenzae. This member of the human saliva microbiota has also been further isolated from various body fluids without formal description of the patients.

Case presentation

We report the case of H. pittmaniae isolate made from a sputum specimen collected from a 58-year-old Caucasian man with a massive fibrotic form of siderosis who was awaiting lung transplantation. Identification of the isolate was ascertained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene sequencing. H. pittmaniae was considered to be responsible for the worsening of the patient’s chronic respiratory failure and was successfully treated with oral amoxicillin.

Conclusion

H. pittmaniae should be regarded as a new pathogen responsible for respiratory tract infection in patients with chronic lung diseases.
Interaction among apoptosis-associated sequence variants and joint effects on aggressive prostate cancer
Authors: Lavender Nicole A , Rogers Erica N , Yeyeodu Susan , Rudd James , Hu Ting , Zhang Jie , Brock Guy N , Kimbro Kevin S , Moore Jason H , Hein David W , Kidd La Creis R
Published: April 2012

Background

Molecular and epidemiological evidence demonstrate that altered gene expression and single nucleotide polymorphisms in the apoptotic pathway are linked to many cancers. Yet, few studies emphasize the interaction of variant apoptotic genes and their joint modifying effects on prostate cancer (PCA) outcomes. An exhaustive assessment of all the possible two-, three- and four-way gene-gene interactions is computationally burdensome. This statistical conundrum stems from the prohibitive amount of data needed to account for multiple hypothesis testing.

Methods

To address this issue, we systematically prioritized and evaluated individual effects and complex interactions among 172 apoptotic SNPs in relation to PCA risk and aggressive disease (i.e., Gleason score ≥ 7 and tumor stages III/IV). Single and joint modifying effects on PCA outcomes among European-American men were analyzed using statistical epistasis networks coupled with multi-factor dimensionality reduction (SEN-guided MDR). The case-control study design included 1,175 incident PCA cases and 1,111 controls from the prostate, lung, colo-rectal, and ovarian (PLCO) cancer screening trial. Moreover, a subset analysis of PCA cases consisted of 688 aggressive and 488 non-aggressive PCA cases. SNP profiles were obtained using the NCI Cancer Genetic Markers of Susceptibility (CGEMS) data portal. Main effects were assessed using logistic regression (LR) models. Prior to modeling interactions, SEN was used to pre-process our genetic data. SEN used network science to reduce our analysis from > 36 million to < 13,000 SNP interactions. Interactions were visualized, evaluated, and validated using entropy-based MDR. All parametric and non-parametric models were adjusted for age, family history of PCA, and multiple hypothesis testing.

Results

Following LR modeling, eleven and thirteen sequence variants were associated with PCA risk and aggressive disease, respectively. However, none of these markers remained significant after we adjusted for multiple comparisons. Nevertheless, we detected a modest synergistic interaction betweenAKT3 rs2125230-PRKCQ rs571715and disease aggressiveness using SEN-guided MDR (p = 0.011).

Conclusions

In summary, entropy-based SEN-guided MDR facilitated the logical prioritization and evaluation of apoptotic SNPs in relation to aggressive PCA. The suggestive interaction betweenAKT3-PRKCQand aggressive PCA requires further validation using independent observational studies.
Human ocular filariasis: further evidence on the zoonotic role of Onchocerca lupi
Authors: Otranto Domenico , Dantas-Torres Filipe , Cebeci Zafer , Yeniad Baris , Buyukbabani Nesimi , Boral Ozden Buyukbaba , Gustinelli Andrea , Mounir Trimèche , Mutafchiev Yasen , Bain Odile
Published: April 2012

Background

Among ocular vector-borne pathogens,Onchocerca volvulus, the agent of the so-called “river blindness”, affects about 37 million people globally. OtherOnchocercaspp. have been sporadically reported as zoonotic agents. Cases of canine onchocerciasis caused byOnchocerca lupiare on the rise in the United States and Europe. Its zoonotic role has been suspected but only recently ascertained in a single case from Turkey. The present study provides further evidence on the occurrence ofO. lupiinfesting human eyes in two patients from Turkey (case 1) and Tunisia (case 2). The importance of obtaining a correct sample collection and preparation of nematodes infesting human eyes is highlighted.

Methods

In both cases the parasites were identified with morpho-anatomical characters at the gross examination, histological analysis and anatomical description and also molecularly in case 1.

Results

The nematode from the first case was obviouslyO. lupibased on their morphology at the gross examination, histological analysis and anatomical description. In the second case, although the diagnostic cuticular characters were not completely developed, other features were congruent with the identification ofO. lupi. Furthermore, the morphological identification was also molecularly confirmed in the Turkish case.

Conclusions

The results of this study suggest thatO. lupiinfestation is not an occasional finding but it should be considered in the differential diagnosis of other zoonotic helminths causing eye infestation in humans (e.g.,D. immitisandDirofilaria repens). Both cases came from areas where no cases of canine onchocerciasis were previously reported in the literature, suggesting that an in depth appraisal of the infestation in canine populations is necessary. Physicians and ophthalmologists are advised on how to preserve nematode samples recovered surgically, to allow a definitive, correct etiological diagnosis.
The conformational flexibility of the C-terminus of histone H4 promotes histone octamer and nucleosome stability and yeast viability
Authors: Chavez Myrriah S , Scorgie Jean K , Dennehey Briana K , Noone Seth , Tyler Jessica K , Churchill Mair EA
Published: April 2012

Background

The protein anti-silencing function 1 (Asf1) chaperones histones H3/H4 for assembly into nucleosomes every cell cycle as well as during DNA transcription and repair. Asf1 interacts directly with H4 through the C-terminal tail of H4, which itself interacts with the docking domain of H2A in the nucleosome. The structure of this region of the H4 C-terminus differs greatly in these two contexts.

Results

To investigate the functional consequence of this structural change in histone H4, we restricted the available conformations of the H4 C-terminus and analyzed its effect in vitro and in vivo in Saccharomyces cerevisiae. One such mutation, H4 G94P, had modest effects on the interaction between H4 and Asf1. However, in yeast, flexibility of the C-terminal tail of H4 has essential functions that extend beyond chromatin assembly and disassembly. The H4 G94P mutation resulted in severely sick yeast, although nucleosomes still formed in vivo albeit yielding diffuse micrococcal nuclease ladders. In vitro, H4G4P had modest effects on nucleosome stability, dramatically reduced histone octamer stability, and altered nucleosome sliding ability.

Conclusions

The functional consequences of altering the conformational flexibility in the C-terminal tail of H4 are severe. Interestingly, despite the detrimental effects of the histone H4 G94P mutant on viability, nucleosome formation was not markedly affected in vivo. However, histone octamer stability and nucleosome stability as well as nucleosome sliding ability were altered in vitro. These studies highlight an important role for correct interactions of the histone H4 C-terminal tail within the histone octamer and suggest that maintenance of a stable histone octamer in vivo is an essential feature of chromatin dynamics.
Orangutan Alu quiescence reveals possible source element: support for ancient backseat drivers
Authors: Walker Jerilyn A , Konkel Miriam K , Ullmer Brygg , Monceaux Christopher P , Ryder Oliver A , Hubley Robert , Smit Arian FA , Batzer Mark A
Published: April 2012

Background

Sequence analysis of the orangutan genome revealed that recent proliferative activity of Alu elements has been uncharacteristically quiescent in the Pongo (orangutan) lineage, compared with all previously studied primate genomes. With relatively few young polymorphic insertions, the genomic landscape of the orangutan seemed like the ideal place to search for a driver, or source element, of Alu retrotransposition.

Results

Here we report the identification of a nearly pristine insertion possessing all the known putative hallmarks of a retrotranspositionally competent Alu element. It is located in an intronic sequence of the DGKB gene on chromosome 7 and is highly conserved in Hominidae (the great apes), but absent from Hylobatidae (gibbon and siamang). We provide evidence for the evolution of a lineage-specific subfamily of this shared Alu insertion in orangutans and possibly the lineage leading to humans. In the orangutan genome, this insertion contains three orangutan-specific diagnostic mutations which are characteristic of the youngest polymorphic Alu subfamily, Alu Ye5b5_Pongo. In the Homininae lineage (human, chimpanzee and gorilla), this insertion has acquired three different mutations which are also found in a single human-specific Alu insertion.

Conclusions

This seemingly stealth-like amplification, ongoing at a very low rate over millions of years of evolution, suggests that this shared insertion may represent an ancient backseat driver of Alu element expansion.
17β-Estradiol Inhibits Iron Hormone Hepcidin Through an Estrogen Responsive Element Half-Site
Authors: Yang Qing , Jian Jinlong , Katz Stuart , Abramson Steven B. , Huang Xi
Published: April 2012

Interaction of estrogen with iron at the systemic level is long suspected, but direct evidence linking the two is limited. In the present study, we examined the effects of 17β-estradiol (E2) on hepcidin, a key negative regulator of iron absorption from the liver. We found that transcription of hepcidin was suppressed by E2 treatment in human liver HuH7 and HepG2 cells, and this down-regulation was blocked by E2 antagonist ICI 182780. Chromatin immunoprecipitation, deletion, and EMSA detected a functional estrogen responsive element half-site that is located between −2474 and −2462 upstream from the start of transcription of the hepcidin gene. After cloning the human hepcidin promoter into the pGL3Luc-Reporter vector, luciferase activity was also down-regulated by E2 treatment in HepG2 cells. E2 reduced hepcidin mRNA in wild-type mice as well as in hemochromatosis Fe gene knockout mice. In summary, our data suggest that hepcidin inhibition by E2 is to increase iron uptake, a mechanism to compensate iron loss during menstruation. This mechanism may also contribute to increased iron stores in oral contraceptive users.
Meiosis-induced alterations in transcript architecture and noncoding RNA expression in S. cerevisiae
Authors: Kim Guisbert Karen S. , Zhang Yong , Flatow Jared , Hurtado Sara , Staley Jonathan P. , Lin Simon , Sontheimer Erik J.
Published: April 2012

Changes in transcript architecture can have powerful effects on protein expression. Regulation of the transcriptome is often dramatically revealed during dynamic conditions such as development. To examine changes in transcript architecture we analyzed the expression and transcript boundaries of protein-coding and noncoding RNAs over the developmental process of meiosis in Saccharomyces cerevisiae. Custom-designed, high-resolution tiling arrays were used to define the time-resolved transcriptome of cells undergoing meiosis and sporulation. These arrays were specifically designed for the S. cerevisiae strain SK1 that sporulates with high efficiency and synchrony. In addition, new methods were created to define transcript boundaries and to identify dynamic changes in transcript expression and architecture over time. Of 8407 total segments, 699 (8.3%) were identified by our algorithm as regions containing potential transcript architecture changes. Our analyses reveal extensive changes to both the coding and noncoding transcriptome, including altered 5′ ends, 3′ ends, and splice sites. Additionally, 3910 (46.5%) unannotated expressed segments were identified. Interestingly, subsets of unannotated RNAs are located across from introns (anti-introns) or across from the junction between two genes (anti-intergenic junctions). Many of these unannotated RNAs are abundant and exhibit sporulation-specific changes in expression patterns. All work, including heat maps of the tiling array, annotation for the SK1 strain, and phastCONS conservation analysis, is available at http://groups.molbiosci.northwestern.edu/sontheimer/sk1meiosis.php. Our high-resolution transcriptome analyses reveal that coding and noncoding transcript architectures are exceptionally dynamic in S. cerevisiae and suggest a vast array of novel transcriptional and post-transcriptional control mechanisms that are activated upon meiosis and sporulation.
Capacity building in the minority ethnic voluntary sector: for whom, how and for what purpose?
Authors: Netto Gina , Kamenou Nicolina , Venugopal Sheetal , Asghar Rabia
Published: April 2012

Changing trends in governance have contributed to the development of ‘capacity-building initiatives’ in the third sector to enable them to take a greater role in partnership approaches, service delivery and social entrepreneurship. However, analysts have argued that such initiatives are more likely to serve the interests of professionalised welfare groups rather than engage with communities’ own skills and interests. Drawing on in-depth individual interviews and case studies with those engaged in such activities in minority ethnic organisations in devolved Scotland, this paper reveals that ‘capacity’ is a socially constructed, negotiated process, which benefits some organisations more than others. We identify factors which are likely to either facilitate or hinder the process. While there is consensus among participants that such activities play a useful role in developing organisational capacity, we argue that the responsibility for addressing structural factors including socio-economic disadvantage and racism remains with government.
Thematic Review: Religion and the Big Society: a match made in heaven?
Authors: Kettell Steven
Published: April 2012

The Big Society agenda forms one of the main programmatic pillars of the Conservative– Liberal Democrat coalition government. Ostensibly based on the principles of decentralisation and empowerment, this envisions a shrinking of the state and a greater role for faith-based organisations in the provision of welfare and social services. For religious groups, involvement with the Big Society is seen as an opportunity to reverse a long-term process of waning social influence and to reshape the role of faith in the public sphere. In the way of these objectives being achieved, however, are a number of serious problems, including the current economic and political situation, the particular characteristics of faith groups themselves and general attitudes towards religion in public life. Given the importance attached to the participation of faith-based organisations in the Big Society project, these issues have significant implications both for the future role of religion in the public sphere and for the unfolding of the programme itself.
Guidelines for reporting of phase equilibrium measurements (IUPAC Recommendations 2012)
Authors: Chirico Robert D. , de Loos Theodoor W. , Gmehling Jürgen , Goodwin Anthony R. H. , Gupta Sumnesh , Haynes William M. , Marsh Kenneth N. , Rives Vicente , Olson James D. , Spencer Calvin , Brennecke Joan F. , Trusler J. P. Martin
Published: April 2012

Recommendations are given for reporting in the primary scientific literature of measurements involving phase equilibrium. The focus is on documentation issues, and many of the recommendations may also be applied to the more general fields of thermodynamic and transport properties. The historical context of the work and specific plans for implementation of the recommendations are discussed.
HIV Sexual Networks: The Montreal Experience
Authors: Brenner Bluma , Moodie Erica E. M.
Published: April 2012

While highly active antiretroviral therapy (HAART) has transformed HIV/AIDS to a chronic, treatable disease in Canada, HIV incidence continues to rise among male-sex-male (MSM) populations. Montreal, Canada, is a unique environment for a comprehensive surveillance study on HIV transmission dynamics. Phylogenetic strategies show that half of all new MSM infections in Montreal may arise through onward transmission by individuals who are in primary HIV infection (PHI) (< 6 months post-infection) and often unaware of their HIV status. Large cluster networks, wherein one infection leads to 5-31 onward transmissions, constitute the fastest-growing sub-epidemic, representing 25% and 39% of genotyped incident infections in 2005 and 2009, respectively. This has disturbing implications in light of the introduction of non-B subtype and drug-resistant sub-epidemics. Biological and behavioural correlates of cluster membership are being investigated to establish risk determinants implicated in the onward transmission of the MSM epidemic. Our findings underscore the opportunities and challenges in implementing new testing and tailored prevention paradigms for different MSM populations.