91 research outputs found
Safety Assessment of Reprogrammed Cells Prior to Clinical Applications: Potential Approaches to Eliminate Teratoma Formation
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ROTATION OF MERCURY: THEORETICAL ANALYSIS OF THE DYNAMICS OF A RIGID ELLIPSOIDAL PLANET
The second-order nonlinear differential equation for the rotation of Mercury is shown to imply locked-in motion when the period is within the range (2T/3) [1-{lambda} cos 2{pi}t/T {+-} 2/3 (21{lambda}e/2){sup 1/2}], where e is the eccentricity and T the period of Mercury's orbit, the time t is measured from perihelion, and {lambda} = (B-A)/C measures the planet's distortion. For values near 2T/3, the instantaneous period oscillates about 2T/3 with period (21{lambda}e/2){sup -1/2}T
A Continuum of Cell States Spans Pluripotency and Lineage Commitment in Human Embryonic Stem Cells
Background: Commitment in embryonic stem cells is often depicted as a binary choice between alternate cell states, pluripotency and specification to a particular germ layer or extraembryonic lineage. However, close examination of human ES cell cultures has revealed significant heterogeneity in the stem cell compartment. Methodology/Principal Findings: We isolated subpopulations of embryonic stem cells using surface markers, then examined their expression of pluripotency genes and lineage specific transcription factors at the single cell level, and tested their ability to regenerate colonies of stem cells. Transcript analysis of single embryonic stem cells showed that there is a gradient and a hierarchy of expression of pluripotency genes in the population. Even cells at the top of the hierarchy generally express only a subset of the stem cell genes studied. Many cells co-express pluripotency and lineage specific genes. Cells along the continuum show a progressively decreasing likelihood of self renewal as their expression of stem cell surface markers and pluripotency genes wanes. Most cells that are positive for stem cell surface markers express Oct-4, but only those towards the top of the hierarchy express the nodal receptor TDGF-1 and the growth factor GDF3. Significance: These findings on gene expression in single embryonic stem cells are in concert with recent studies of early mammalian development, which reveal molecular heterogeneity and a stochasticity of gene expression in blastomeres. Our work indicates that only a small fraction of the population resides at the top of the hierarchy, that lineage priming (co-expression of stem cell and lineage specific genes) characterizes pluripotent stem cell populations, and that extrinsic signaling pathways are upstream of transcription factor networks that control pluripotency
Comparison of non-invasive to invasive oxygenation ratios for diagnosing acute respiratory distress syndrome following coronary artery bypass graft surgery: a prospective derivation-validation cohort study
Objective: To determine if non-invasive oxygenation indices, namely peripheral capillary oxygen saturation (SpO2)/
fraction of inspired oxygen (Fi
O2) and partial pressure of alveolar oxygen (PAO2)/Fi
O2 may be used as effective
surrogates for the partial pressure of arterial oxygen (PaO2)/Fi
O2. Also, to determine the SpO2/Fi
O2 and PAO2/Fi
O2
values that correspond to PaO2/Fi
O2 thresholds for identifying acute respiratory distress syndrome (ARDS) in
patients following coronary artery bypass graft (CABG) surgery.
Methods: A prospective derivation-validation cohort study in the Open-Heart ICU of an academic teaching hospital.
Recorded variables included patient demographics, ventilator settings, chest radiograph results, and SPO2, PaO2,
PAO2, SaO2, and Fi
O2. Linear regression modeling was used to quantify the relationship between indices. Receiver
operating characteristic (ROC) curves were used to determine the sensitivity and specificity of the threshold values.
Results: One-hundred seventy-five patients were enrolled in the derivation cohort, and 358 in the validation
cohort. The SPO2/Fi
O2 and PAO2/Fi
O2 ratios could be predicted well from PaO2/Fi
O2, described by the linear
regression models SPO2/Fi
O2 = 71.149 + 0.8PF and PAO2/Fi
O2 = 38.098 + 2.312PF, respectively. According to the linear
regression equation, a PaO2/Fi
O2 ratio of 300 equaled an SPO2/Fi
O2 ratio of 311 (R2 0.857, F 1035.742, < 0.0001) and
a PAO2/Fi
O2 ratio of 732 (R2 0.576, F 234.887, < 0.0001). The SPO2/Fi
O2 threshold of 311 had 90% sensitivity, 80%
specificity, LR+ 4.50, LR- 0.13, PPV 98, and NPV 42.1 for the diagnosis of mild ARDS. The PAO2/Fi
O2 threshold of 732
had 86% sensitivity, 90% specificity, LR+ 8.45, LR- 0.16, PPV 98.9, and NPV 36 for the diagnosis of mild ARDS. SPO2/
Fi
O2 had excellent discrimination ability for mild ARDS (AUC ± SE = 0.92 ± 0.017; 95% CI 0.889 to 0.947) as did PAO2/
Fi
O2 (AUC ± SE = 0.915 ± 0.018; 95% CI 0.881 to0.942). Conclusions: PaO2 and SaO2 correlated in the diagnosis of ARDS, with a PaO2/Fi
O2 of 300 correlating to an SPO2/
Fi
O2 of 311 (Sensitivity 90%, Specificity 80%). The SPO2/ Fi
O2 ratio may allow for early real-time rapid identification of
ARDS, while decreasing the cost, phlebotomy, blood loss, pain, skin breaks, and vascular punctures associated with
serial arterial blood gas measurements
A Shigella boydii bacteriophage which resembles Salmonella phage ViI
<p>Abstract</p> <p>Background</p> <p>Lytic bacteriophages have been applied successfully to control the growth of various foodborne pathogens. Sequencing of their genomes is considered as an important preliminary step to ensure their safety prior to food applications.</p> <p>Results</p> <p>The lytic bacteriophage, ΦSboM-AG3, targets the important foodborne pathogen, <it>Shigella</it>. It is morphologically similar to phage ViI of <it>Salmonella enterica </it>serovar Typhi and a series of phages of <it>Acinetobacter calcoaceticus </it>and <it>Rhizobium meliloti</it>. The complete genome of ΦSboM-AG3 was determined to be 158 kb and was terminally redundant and circularly permuted. Two hundred and sixteen open reading frames (ORFs) were identified and annotated, most of which displayed homology to proteins of <it>Salmonella </it>phage ViI. The genome also included four genes specifying tRNAs.</p> <p>Conclusions</p> <p>This is the first time that a Vi-specific phage for <it>Shigella </it>has been described. There is no evidence for the presence of virulence and lysogeny-associated genes. In conclusion, the genome analysis of ΦSboM-AG3 indicates that this phage can be safely used for biocontrol purposes.</p
Genomic, Proteomic and Physiological Characterization of a T5-like Bacteriophage for Control of Shiga Toxin-Producing Escherichia coli O157:H7
Despite multiple control measures, Escherichia coli O157:H7 (STEC O157:H7) continues to be responsible for many food borne outbreaks in North America and elsewhere. Bacteriophage therapy may prove useful for controlling this pathogen in the host, their environment and food. Bacteriophage vB_EcoS_AKFV33 (AKFV33), a T5-like phage of Siphoviridae lysed common phage types of STEC O157:H7 and not non-O157 E. coli. Moreover, STEC O157:H7 isolated from the same feedlot pen from which the phage was obtained, were highly susceptible to AKFV33. Adsorption rate constant and burst size were estimated to be 9.31×10−9 ml/min and 350 PFU/infected cell, respectively. The genome of AKVF33 was 108,853 bp (38.95% G+C), containing 160 open reading frames (ORFs), 22 tRNA genes and 32 strong promoters recognized by host RNA polymerase. Of 12 ORFs without homologues to T5-like phages, 7 predicted novel proteins while others exhibited low identity (<60%) to proteins in the National Centre for Biotechnology Information database. AKVF33 also lacked the L-shaped tail fiber protein typical of T5, but was predicted to have tail fibers comprised of 2 novel proteins with low identity (37–41%) to tail fibers of E. coli phage phiEco32 of Podoviridae, a putative side tail fiber protein of a prophage from E. coli IAI39 and a conserved domain protein of E. coli MS196-1. The receptor-binding tail protein (pb5) shared an overall identify of 29–72% to that of other T5-like phages, with no region coding for more than 6 amino acids in common. Proteomic analysis identified 4 structural proteins corresponding to the capsid, major tail, tail fiber and pore-forming tail tip (pb2). The genome of AKFV33 lacked regions coding for known virulence factors, integration-related proteins or antibiotic resistance determinants. Phage AKFV33 is a unique, highly lytic STEC O157:H7-specific T5-like phage that may have considerable potential as a pre- and post-harvest biocontrol agent
A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis
Introduction: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. Methods: A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. Results: In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Conclusion: Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. Systematic review: PROSPERO registration number: CRD 4201300500
Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage
The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells
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