Abstract Preterm birth is associated with elevated production of pro-inflammatory cytokines such as TNFα at the maternal–fetal interface. Previous studies have suggested that women with a history of ...preterm birth produce aberrantly strong inflammatory responses to bacterial lipopolysaccharide (LPS). However many intrauterine infections in women are associated with pathogens including Ureaplasma urealyticum , Mycoplasma hominis and Streptococcus agalactiae (group B streptococcus) that contain pro-inflammatory factors other than LPS. We evaluated whether peripheral blood leukocytes from women with a history of preterm birth produce elevated amounts of TNFα upon stimulation with pathogens associated with preterm birth and if pre-treatment with aspirin, an anti-inflammatory medication, decreases the ex vivo production of this cytokine. Heat-killed bacteria elicited increased TNFα production from leukocytes in a dose-dependent manner, but no differences in TNFα production between leukocytes from women with preterm birth and control women with term birth were detected. In women who consumed aspirin each day for one week, TNFα production was increased in leukocytes from control women stimulated with Escherichia coli and U. urealyticum , but was reduced or unchanged in leukocytes from women with preterm birth. Similar trends were observed for a subset of samples stimulated with U. urealyticum and assayed for IL-6, IL-10, IL-1β and TNFα by bead array. We conclude that leukocytes from women with a history of preterm birth do not have elevated pro-inflammatory responses to pathogens, and that reproductive history is associated with different effects of aspirin on pro-inflammatory cytokine production.
Abstract Lipopolysaccharide (LPS)-stimulated TNFα production is reported to be greater for whole blood (WB) cultures prepared from patients with a history of preterm birth than cultures obtained from ...women with a history of term birth. The objectives of this study were (1) to determine if there is a similar differential responsiveness for peripheral blood mononuclear leukocytes (PBML) and (2) to determine if treatment with aspirin influences LPS-stimulated TNFα production in these patients. WB and PBML were obtained from women with a history of preterm delivery before 32 weeks (cases; n = 5) and age- and race-matched controls ( n = 5) with a history of uncomplicated term delivery. WB and PBML were cultured and stimulated with LPS. All participants then took aspirin daily for 1 week and responsiveness of PBML and WB cultures to LPS was retested. The history of preterm labor was found to have no effect on LPS-stimulated TNFα production in cultures of WB or PBML. Aspirin treatment enhanced LPS-stimulated TNFα production by PBML from controls but not cases. We conclude that endotoxin responsiveness of women with a history of preterm birth is similar to that of women with a history of term birth in terms of in vitro TNFα production. Aspirin increases TNFα production by PBML in control women but not in women with a history of preterm birth. The divergent responses to aspirin treatment in patients with and without prior preterm labor may reflect differential regulation of cytokine production by prostaglandins in women with preterm labor associated with infection or inflammation.
Objective: We determined whether changes in sodium pump isoform abundance accompanied active human labor. Study Design: Specimens of placenta, amniochorion, and myometrium were collected from women ...in active spontaneous labor and from those not in labor. The abundance of the three sodium pump α-isoforms was determined by Western blot analysis. Results: Levels of the α1 and α2 isoforms were comparable in the three tissues for women in labor and not in labor. However, α3 isoform abundance in placenta and myometrium (but not amniochorion) was significantly decreased in women in active labor compared with women not in labor (sodium pump α3 in placenta: no labor 91.2 ± 27.6 vs labor 46.9 ± 3.6 density units, P =.002. Sodium pump α3 in myometrium: no labor 52.3 ± 7.7 vs labor 19.8 ± 1.6 density units, P =.0002). Conclusion: Because reductions in sodium pump number can result in hormone release from secretory tissues and in contraction of muscle, this suggests that the sodium pump may play a significant role in the initiation or maintenance of human labor. (Am J Obstet Gynecol 2003;188:759-64.)
Lipopolysaccharide (LPS)-stimulated TNFalpha production is reported to be greater for whole blood (WB) cultures prepared from patients with a history of preterm birth than cultures obtained from ...women with a history of term birth. The objectives of this study were (1) to determine if there is a similar differential responsiveness for peripheral blood mononuclear leukocytes (PBML) and (2) to determine if treatment with aspirin influences LPS-stimulated TNFalpha production in these patients. WB and PBML were obtained from women with a history of preterm delivery before 32 weeks (cases; n=5) and age- and race-matched controls (n=5) with a history of uncomplicated term delivery. WB and PBML were cultured and stimulated with LPS. All participants then took aspirin daily for 1 week and responsiveness of PBML and WB cultures to LPS was retested. The history of preterm labor was found to have no effect on LPS-stimulated TNFalpha production in cultures of WB or PBML. Aspirin treatment enhanced LPS-stimulated TNFalpha production by PBML from controls but not cases. We conclude that endotoxin responsiveness of women with a history of preterm birth is similar to that of women with a history of term birth in terms of in vitro TNFalpha production. Aspirin increases TNFalpha production by PBML in control women but not in women with a history of preterm birth. The divergent responses to aspirin treatment in patients with and without prior preterm labor may reflect differential regulation of cytokine production by prostaglandins in women with preterm labor associated with infection or inflammation.
AlphaSim: Software for Breeding Program Simulation Faux, Anne‐Michelle; Gorjanc, Gregor; Gaynor, R. Chris ...
The plant genome,
November 2016, 2016-11-00, 20161101, 2016-11-01, Letnik:
9, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Core Ideas
AlphaSim allows breeders and researchers to simulate genomic data with specific user criteria.
AlphaSim is flexible, computationally efficient, and easy to use for a wide range of possible ...scenarios.
AlphaSim can also be used in animal breeding, human genetics, and population genetics.
This paper describes AlphaSim, a software package for simulating plant and animal breeding programs. AlphaSim enables the simulation of multiple aspects of breeding programs with a high degree of flexibility. AlphaSim simulates breeding programs in a series of steps: (i) simulate haplotype sequences and pedigree; (ii) drop haplotypes into the base generation of the pedigree and select single‐nucleotide polymorphism (SNP) and quantitative trait nucleotide (QTN); (iii) assign QTN effects, calculate genetic values, and simulate phenotypes; (iv) drop haplotypes into the burn‐in generations; and (v) perform selection and simulate new generations. The program is flexible in terms of historical population structure and diversity, recent pedigree structure, trait architecture, and selection strategy. It integrates biotechnologies such as doubled‐haploids (DHs) and gene editing and allows the user to simulate multiple traits and multiple environments, specify recombination hot spots and cold spots, specify gene jungles and deserts, perform genomic predictions, and apply optimal contribution selection. AlphaSim also includes restart functionalities, which increase its flexibility by allowing the simulation process to be paused so that the parameters can be changed or to import an externally created pedigree, trial design, or results of an analysis of previously simulated data. By combining the options, a user can simulate simple or complex breeding programs with several generations, variable population structures and variable breeding decisions over time. In conclusion, AlphaSim is a flexible and computationally efficient software package to simulate biotechnology enhanced breeding programs with the aim of performing rapid, low‐cost, and objective in silico comparison of breeding technologies.
Phytoplankton growth rates are limited by the supply of iron (Fe) in approximately one third of the open ocean, with major implications for carbon dioxide sequestration and carbon (C) ...biogeochemistry. To date, understanding how alteration of Fe supply changes phytoplankton physiology has focused on traditional metrics such as growth rate, elemental composition, and biophysical measurements such as photosynthetic competence (Fv/Fm). Researchers have subsequently employed transcriptomics to probe relationships between changes in Fe supply and phytoplankton physiology. Recently, studies have investigated longer-term (i.e. following acclimation) responses of phytoplankton to various Fe conditions. In the present study, the coastal diatom, Thalassiosira pseudonana, was acclimated (10 generations) to either low or high Fe conditions, i.e. Fe-limiting and Fe-replete. Quantitative proteomics and a newly developed proteomic profiling technique that identifies low abundance proteins were employed to examine the full complement of expressed proteins and consequently the metabolic pathways utilized by the diatom under the two Fe conditions. A total of 1850 proteins were confidently identified, nearly tripling previous identifications made from differential expression in diatoms. Given sufficient time to acclimate to Fe limitation, T. pseudonana up-regulates proteins involved in pathways associated with intracellular protein recycling, thereby decreasing dependence on extracellular nitrogen (N), C and Fe. The relative increase in the abundance of photorespiration and pentose phosphate pathway proteins reveal novel metabolic shifts, which create substrates that could support other well-established physiological responses, such as heavily silicified frustules observed for Fe-limited diatoms. Here, we discovered that proteins and hence pathways observed to be down-regulated in short-term Fe starvation studies are constitutively expressed when T. pseudonana is acclimated (i.e., nitrate and nitrite transporters, Photosystem II and Photosystem I complexes). Acclimation of the diatom to the desired Fe conditions and the comprehensive proteomic approach provides a more robust interpretation of this dynamic proteome than previous studies.
To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes.
Participants were recruited from the Primary Research in ...Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22).
Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 95% CI 1.03-2.21). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 1.05-4.75). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 0.19-0.92).
Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.
PDF
