Browsing by Title

Sort by: Order: Results:

Now showing items 55-60 of 60
  • Seo, Seung Bum; Zeng, Xiangpei; King, Jonathan L; Larue, Bobby L; Assidi, Mourad; Al-Qahtani, Mohamed H; Sajantila, Antti; Budowle, Bruce (BioMed Central Ltd, 2015)
    Abstract Background Massively parallel sequencing (MPS) technologies have the capacity to sequence targeted regions or whole genomes of multiple nucleic acid samples with high coverage by sequencing millions of DNA fragments simultaneously. Compared with Sanger sequencing, MPS also can reduce labor and cost on a per nucleotide basis and indeed on a per sample basis. In this study, whole genomes of human mitochondria (mtGenome) were sequenced on the Personal Genome Machine (PGMTM) (Life Technologies, San Francisco, CA), the out data were assessed, and the results were compared with data previously generated on the MiSeqTM (Illumina, San Diego, CA). The objectives of this paper were to determine the feasibility, accuracy, and reliability of sequence data obtained from the PGM. Results 24 samples were multiplexed (in groups of six) and sequenced on the at least 10 megabase throughput 314 chip. The depth of coverage pattern was similar among all 24 samples; however the coverage across the genome varied. For strand bias, the average ratio of coverage between the forward and reverse strands at each nucleotide position indicated that two-thirds of the positions of the genome had ratios that were greater than 0.5. A few sites had more extreme strand bias. Another observation was that 156 positions had a false deletion rate greater than 0.15 in one or more individuals. There were 31-98 (SNP) mtGenome variants observed per sample for the 24 samples analyzed. The total 1237 (SNP) variants were concordant between the results from the PGM and MiSeq. The quality scores for haplogroup assignment for all 24 samples ranged between 88.8%-100%. Conclusions In this study, mtDNA sequence data generated from the PGM were analyzed and the output evaluated. Depth of coverage variation and strand bias were identified but generally were infrequent and did not impact reliability of variant calls. Multiplexing of samples was demonstrated which can improve throughput and reduce cost per sample analyzed. Overall, the results of this study, based on orthogonal concordance testing and phylogenetic scrutiny, supported that whole mtGenome sequence data with high accuracy can be obtained using the PGM platform.
  • Myllärniemi, Marjukka; Tikkanen, Jussi; Hulmi, Juha J; Pasternack, Arja; Sutinen, Eva; Rönty, Mikko; Leppäranta, Outi; Ma, Hongqiang; Ritvos, Olli; Koli, Katri (BioMed Central Ltd, 2014)
    Abstract Background Activins are members of the TGF-ß superfamily of growth factors. First, we identified by expression array screening that activin-B and follistatin are upregulated in human idiopathic pulmonary fibrosis (IPF). Next, we wanted to clarify their specific role in lung fibrosis formation. Methods We used specific antibodies for activin-A and -B subunits and follistatin to measure and localize their levels in idiopathic pulmonary fibrosis and control lung biopsies. To inhibit activin signaling, we used soluble activin type IIB receptor fused to the Fc portion of human IgG1 (sActRIIB-Fc) in two different mouse models of pulmonary fibrosis. Results Activin-B and follistatin mRNA levels were elevated in the human IPF lung. Immunoreactivity to activin-A, -B and follistatin localized predominantly to the hyperplastic, activated alveolar epithelium, but was also seen in inflammatory cells. Mice treated with sActRIIB-Fc showed increased skeletal muscle mass and a clear reduction in alveolar cell counts in bronchoalveolar lavage fluid, but no significant antifibrotic effect in the lung was observed. Conclusions The upregulation of activin-B and follistatin in IPF is a novel finding. Our results indicate that activin inhibition is not an efficient tool for antifibrotic therapy, but could be useful in reducing alveolar cellular response to injury. Activin-B and follistatin levels may be useful as biomarkers of IPF.
  • van de Bunt, Bert; Bron, Peter A; Sijtsma, Lolke; de Vos, Willem M; Hugenholtz, Jeroen (BioMed Central Ltd, 2014)
    Abstract Background Lactococcus lactis is a lactic acid bacterium that has been used for centuries in the production of a variety of cheeses, as these bacteria rapidly acidify milk and greatly contribute to the flavour of the fermentation end-products. After a short growth phase during cheese ripening L. lactis enters an extended non-growing state whilst still strongly contributing to amino acid-derived flavour formation. Here, a research approach is presented that allows investigation of strain- and amino acid-specific flavour formation during the non-growing state. Results Non-growing cells of five selected L. lactis strains were demonstrated to degrade amino acids into flavour compounds that are relevant in food fermentations and differs greatly from production of flavour compounds using growing cells. As observed earlier in other research set-ups and with other microorganisms, addition of NADH, α-ketoglutarate and pyridoxal-5-phosphate was demonstrated to be essential for optimal flavour formation, suggesting that intracellular pools of these substrates are too low for the significant production of the flavour compounds. Production of flavours during the non-growing phase strongly depends on the individual amino acids that were supplied, on the presence of other amino acids (mixtures versus single compounds), and on the strain used. Moreover, we observed that the plasmid-free model strains L. lactis MG1363 and IL1403 produce relatively low amounts of flavour components under the various conditions tested. Conclusions By using this simplified and rapid approach to study flavour formation by non-growing lactic acid bacteria, lengthy ripening periods are no longer required to assess the capacity of strains to produce flavours in the long, non-growing state of dairy fermentation. In addition, this method also provides insight into the conversion of single amino acids versus the conversion of a mixture of amino acids as produced during protein degradation. The generated results are complementary to earlier generated datasets using growing cells, allowing assessment of the full flavour forming potential of strains used as starter cultures in industrial food fermentation processes.
  • Hemminki, Elina; Virtanen, Jorma I; Veerus, Piret (BioMed Central Ltd, 2014)
    Abstract Background To present empirical data on how the variation in regulating clinical research and patient care was perceived in Finland between 2009 and 2012. Methods Notes of interviews with 22 research ethics committee (REC) chairpersons were analyzed to identify whether differences in the regulation of clinical research and patient care were addressed. REC chairpersons’ opinions on three imaginary cases of clinical research projects challenging current research ethics rules (vignettes) were requested with a questionnaire; 18 of the 22 interviewed chairpersons responded. Results Based on REC chairpersons’ interviews, the differences between care and research regulation were not considered important issues in Finland. In the vignettes, REC chairpersons’ assumptions on how their REC would decide varied in regard to allowing research without informed consent, while solutions that are not allowed by current law were even anticipated. Mostly, but not always, the chairpersons’ own personal view agreed with their REC. Conclusions The distinction between care and research regulation has not been publicly challenged by Finnish RECs, even though it is a challenge when research relevant to health care is carried out. There is a need for debate and changes in laws and practices.
  • Hemilä, Harri; Al-Biltagi, Mohammed; Baset, Ahmed A (BioMed Central Ltd, 2011)
    Abstract Background We previously found a significant benefit of vitamin C supplementation in asthmatic children. Purpose To test whether the effect of vitamin C on asthma is heterogeneous over the participant population. Methods Egyptian asthmatic children between 7 and 10 years of age (n = 60) were included in the cross-over trial. They were administered 0.2 grams per day of vitamin C and placebo for separate 6-week periods. The variation in the vitamin C effect on two clinically relevant outcomes was analyzed: the childhood asthma control test (C-ACT), which measures the severity of asthma symptoms (the scale ranges from 0 to 27 points, < 20 points indicating unsatisfactory asthma control), and FEV1. We used linear modeling to examine the variation of the vitamin C effect in the subgroups. Results The effect of vitamin C on the C-ACT was significantly modified by age and baseline C-ACT levels. In the children aged 7.0-8.2 years with a baseline C-ACT of 18 to 19 points, vitamin C increased the C-ACT score by 4.2 points (95% CI: 3.3-5.3); whereas in the children aged 8.3-10 years who had a baseline C-ACT of 14 to 15 points, vitamin C increased the C-ACT score by only 1.3 points (95% CI: 0.1-2.5). The effect of vitamin C on the FEV1 levels was significantly modified by age and exposure to dampness. In the children aged 7.0-8.2 years with no exposure to dampness, vitamin C increased the FEV1 level by 37% (95% CI: 34-40%), whereas in the children aged 8.3-10 years with exposure to dampness or mold in their bedroom more than one year prior to the study, vitamin C increased the FEV1 level by only 21% (95% CI: 18-25%). Conclusions We found strong evidence that the effect of vitamin C on asthmatic children is heterogeneous. Further research is needed to confirm our findings and identify the groups of children who would receive the greatest benefit from vitamin C supplementation.
  • Sartelli, Massimo; Viale, Pierluigi; Koike, Kaoru; Pea, Federico; Tumietto, Fabio; van Goor, Harry; Guercioni, Gianluca; Nespoli, Angelo; Tranà, Cristian; Catena, Fausto; Ansaloni, Luca; Leppaniemi, Ari; Biffl, Walter; Moore, Frederick A; Poggetti, Renato; Pinna, Antonio D; Moore, Ernest E (BioMed Central Ltd, 2011)
    Abstract Intra-abdominal infections are still associated with high rate of morbidity and mortality. A multidisciplinary approach to the management of patients with intra-abdominal infections may be an important factor in the quality of care. The presence of a team of health professionals from various disciplines, working in concert, may improve efficiency, outcome, and the cost of care. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bologna on July 2010, during the 1st congress of the WSES, involving surgeons, infectious disease specialists, pharmacologists, radiologists and intensivists with the goal of defining recommendations for the early management of intra-abdominal infections. This document represents the executive summary of the final guidelines approved by the consensus conference.