Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes.

ObjectiveIn mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL function, prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.Research design and methodsHDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography-tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.ResultsThe HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).ConclusionsIn patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired

Apolipoprotein A-I Mimetic Peptides Prevent Atherosclerosis Development and Reduce Plaque Inflammation in a Murine Model of Diabetes

ObjectiveTo determine the effect of the apolipoprotein A-I (ApoA-I) mimetic peptide, D-4F, on atherosclerosis development in a pre-existing diabetic condition.Research design and methodsWe induced hyperglycemia in 6-week-old apoE(-/-) female mice using streptozotocin. Half of the diabetic apoE(-/-) mice received D-4F in drinking water. Ten weeks later, plasma lipids, glucose, insulin levels, atherosclerotic lesions, and lesion macrophage content were measured.ResultsDiabetic apoE(-/-) mice developed ∼300% more lesion area, marked dyslipidemia, increased glucose levels, and reduced plasma insulin levels when compared with nondiabetic apoE(-/-) mice. Atherosclerotic lesions were significantly reduced in the D-4F-treated diabetic apoE(-/-) mice in whole aorta (1.11 ± 0.73 vs. 0.58 ± 0.44, percentage of whole aorta, P < 0.01) and in aortic roots (36,038 ± 18,467 μm²/section vs. 17,998 ± 12,491 μm²/section, P < 0.01) when compared with diabetic apoE(-/-) mice that did not receive D-4F. Macrophage content in atherosclerotic lesions from D-4F-treated diabetic apoE(-/-) mice was significantly reduced when compared with nontreated animals (78.03 ± 26.1 vs. 29.6 ± 15.2 P < 0.001, percentage of whole plaque). There were no differences in glucose, insulin, total cholesterol, HDL cholesterol, and triglyceride levels between the two groups. Arachidonic acid, PGE₂, PGD₂, 15-HETE, 12-HETE, and 13-HODE concentrations were significantly increased in the liver tissue of diabetic apoE(-/-) mice compared with nondiabetic apoE(-/-) mice and significantly reduced by D-4F treatment.ConclusionsOur results suggest that oral D-4F can prevent atherosclerosis development in pre-existing diabetic mice and this is associated with a reduction in hepatic arachidonic acid and oxidized fatty acid levels

High cycle fatigue analysis in the presence of autofrettage compressive residual stress

An experimental and numerical investigation of the effect of residual compressive stress on the high cycle fatigue life of notched low carbon steel test specimens is presented. Experimentally determined cyclic stress strain curves for S355 low carbon steel are utilized in a Finite Element Analysis plasticity modelling framework incorporating a new cyclic plasticity material model representative of cyclic hardening and softening, cyclic mean stress relaxation and ratcheting behaviors. Fatigue test results are presented for standard tensile fatigue test specimens and novel double notch specimens. Double notch specimens are tested with and without compressive residual stress prior-induced through tensile overload. It is shown that cyclic plasticity phenomena have a significant influence on the induced residual stress distribution and also on material behavior when fatigue tested in the high cycle regime. It is observed that higher initial compressive residual stresses magnitude does not necessarily lead to a longer fatigue life. Finite Element Analysis using the new cyclic plasticity material model shows this behavior is due to combined residual stress redistribution under fatigue test cyclic loading and cyclic hardening effects. A fatigue life methodology based on the stress-life approach augmented by a critical distance method is proposed and shown to give good agreement with experimental results for test specimens with no induced residual stress. The results obtained for specimens with induced residual stress are more conservative but the degree of conservatism is significantly lower than that in the conventional stress life approach. The proposed methodology is therefore suitable for analysis and design assessment of components with pre-service induced compressive residual stress, such as autofrettaged pressure components

Human resident liver myeloid cells protect against metabolic stress in obesity

Although multiple populations of macrophages have been described in the human liver, their function and turnover in patients with obesity at high risk of developing non-alcoholic fatty liver disease (NAFLD) and cirrhosis are currently unknown. Herein, we identify a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation, we find that liver myeloid cell turnover differs between humans and mice. Using single-cell techniques and flow cytometry, we determine that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures reveal that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD

Risk and Ethical Concerns of Hunting Male Elephant: Behavioural and Physiological Assays of the Remaining Elephants

BACKGROUND: Hunting of male African elephants may pose ethical and risk concerns, particularly given their status as a charismatic species of high touristic value, yet which are capable of both killing people and damaging infrastructure. METHODOLOGY/PRINCIPAL FINDINGS: We quantified the effect of hunts of male elephants on (1) risk of attack or damage (11 hunts), and (2) behavioural (movement dynamics) and physiological (stress hormone metabolite concentrations) responses (4 hunts) in Pilanesberg National Park. For eleven hunts, there were no subsequent attacks on people or infrastructure, and elephants did not break out of the fenced reserve. For three focal hunts, there was an initial flight response by bulls present at the hunting site, but their movements stabilised the day after the hunt event. Animals not present at the hunt (both bulls and herds) did not show movement responses. Physiologically, hunting elephant bulls increased faecal stress hormone levels (corticosterone metabolites) in both those bulls that were present at the hunts (for up to four days post-hunt) and in the broader bull and breeding herd population (for up to one month post-hunt). CONCLUSIONS/SIGNIFICANCE: As all responses were relatively minor, hunting male elephants is ethically acceptable when considering effects on the remaining elephant population; however bulls should be hunted when alone. Hunting is feasible in relatively small enclosed reserves without major risk of attack, damage, or breakout. Physiological stress assays were more effective than behavioural responses in detecting effects of human intervention. Similar studies should evaluate intervention consequences, inform and improve best practice, and should be widely applied by management agencies

Contributo alla conoscenza demografica della Somalia sotto amministrazione fiduciaria italiana

Note sulle statistiche della popolazione autoctona della Somalia: cenni ai censimenti precedenti il periodo dell'AFIS e analisi approfondita dell'organizzazione e dei risultati della prima rilevazione demografica effettuata nel paese.Warbixin kooban oo ku saabsan tirakoobka dadka ab'ogaaga ah ee Soomaaliya: war kooban oo ku saabsan tirakoobkii ka horreeyay xilligii AFIS (walaayadii Taliyaaniga) iyo falanqayn ku saabsan abaabulka iyo natiijadii tirakoobka ugu horreeyay ee ka dhaca dalka Soomaaliyeed.Notes on the statistics about native Somali population: the censuses before Italian Trasteeship are mentioned; an in-depth analysis is conducted about the organisation and the results of the first experience of the demographic account in the country

SEX AND AGE DIFFERENTIAL IN SEASONAL HOME RANGE SIZE OF MOOSE IN NORTHCENTRAL ALBERTA, 1971-1979

Analysis of 277 home ranges of moose (Alces alces) in northcentral Alberta showed sex- and age-specific differences in seasonal home ranges, in spite of large individual variability. Subadults (yearlings and two-year-olds) had larger home ranges than adults. The difference was found to be largely attributable to subadult males. Summer ranges of yearling males and females averaged 29.7 and 4.9 km2, respectively. Home ranges of two-year-old males averaged 25.9 km2 during summer and 47.9 km2 during fall, while two-year-old females averaged 7.5 and 10.9 km2, respectively. Of the entire male population, only two-year-olds had considerably large home ranges in the fall. Overall, moose inhabiting the Swan Hills study area had markedly larger home ranges than previously reported in other regions. The difference was related to the high degree of habitat interspersion in the boreal environments in northcentral Alberta, and to the resulting wide dispersion of food and cover resources. Winter home ranges were significantly larger than home ranges during other seasons, reflecting the limited availability of browse species