| 1. |
- Ganda, Anjali, et al.
(författare)
-
Plasma metabolite profiles, cellular cholesterol efflux, and non-traditional cardiovascular risk in patients with CKD
- 2017
-
Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 1095-8584 .- 0022-2828. ; 112, s. 114-122
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that cholesterol efflux in humans would vary in terms of cellular components, with potential implications for cardiovascular disease.METHODS: We recruited 120 CKD patients (eGFR<30mL/min/1.73m(2)) and 120 control subjects (eGFR ≥60mL/min/1.73m(2)) in order to measure cholesterol efflux using either patients' HDL and THP-1 macrophages or patients' monocytes and a flow cytometry based cholesterol efflux assay. We also measured cell-surface levels of the common β subunit of the IL-3/GM-CSF receptor (IL-3Rβ) which has been linked to defective cholesterol homeostasis and may promote monocytosis. In addition, we measured plasma inflammatory cytokines and plasma metabolite profiles.RESULTS: There was a strong positive correlation between cell-surface IL-3Rβ levels and monocyte counts in CKD (P<0.001). ABCA1 mRNA was reduced in CKD vs. control monocytes (P<0.05), across various etiologies of CKD. Cholesterol efflux to apolipoprotein A1 was impaired in monocytes from CKD patients with diabetic nephropathy (P<0.05), but we found no evidence for a circulating HDL-mediated defect in cholesterol efflux in CKD. Profiling of plasma metabolites showed that medium-chain acylcarnitines were both independently associated with lower levels of cholesterol transporter mRNA in CKD monocytes at baseline (P<0.05), and with cardiovascular events in CKD patients after median 2.6years of follow-up.CONCLUSIONS: Cholesterol efflux in humans varies in terms of cellular components. We report a cellular defect in ABCA1-mediated cholesterol efflux in monocytes from CKD patients with diabetic nephropathy. Unlike several traditional risk factors for atherosclerotic cardiovascular disease, plasma metabolites inversely associated with endogenous cholesterol transporters predicted cardiovascular events in CKD patients. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
|
|
| 2. |
- Hogan, Linda, et al.
(författare)
-
How often is a low 5-min Apgar score in term newborns due to asphyxia?
- 2007
-
Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115. ; 130:2, s. 169-175
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate how often low 5-min Apgar scores (AS(5-min)) at term are associated with asphyxia. Study design: A cohort- and case-control study, including all 183 term infants with AS(5-min) below 7 born at Lund University Hospital during 1993-2002, antepartum deaths excluded. The control group included 183 randomly selected term newborns with AS(5-min) 9-10. Cardiotocography (CTG) traces were assessed blinded to group and outcome. Obstetric and pediatric files were reviewed. Results: After excluding infants with severe malformations, indications of hypoxia were found at the following rates in cases with AS(5-min) below 4 (N = 30), scores 4-6 (N = 143), and controls (N = 182)-abnormal admission CTG: 38%, 8% and 0.6%; abnormal CTG before birth: 88%, 69% and 18%; obstetrical catastrophe: 28%, 6% and 0.6%; interventions for fetal distress: 83%, 48% and 9%; cord artery pH below 7.15: 69%, 54% and 7%; hypoxic ischemic encephalopathy or hypoxic death: 70%, 14% and none. All differences between each case group and controls were statistically significant (p < 0.0001). Conclusions: In the absence of severe malformations, the vast majority of AS(5-min) below 4, and at least half of scores 4-6 could be attributed to birth asphyxia. Signs of hypoxia usually appeared during labor, but were present at admission in 38% of cases with AS(5-min) below 4.
|
|
| 3. |
- Nene, Vishvanath, et al.
(författare)
-
Genome sequence of Aedes aegypti, a major arbovirus vector.
- 2007
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
-
Tidskriftsartikel (refereegranskat)abstract
- We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
|
|
| 4. |
- Wampach, Linda, et al.
(författare)
-
Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life
- 2017
-
Ingår i: Frontiers in Microbiology. - : Frontiers Research Foundation. - 1664-302X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.
|
|
