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Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice

RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles




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Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews




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Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis

IJ Goldberg
Apr 1, 1996; 37:693-707
Reviews




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The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function

JP Segrest
Feb 1, 1992; 33:141-166
Reviews




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Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI

JE Hixson
Mar 1, 1990; 31:545-548
Articles




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Existence and uniqueness result for reaction-diffusion model of diffusive population dynamics

A. Kh. Khachatryan, Kh. A. Khachatryan and A. Zh. Narimanyan
Trans. Moscow Math. Soc. 83 (), 183-200.
Abstract, references and article information




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Populism Comes to South Korea

Populism Comes to South Korea Expert comment sysadmin 20 December 2016

Public disgust with the embattled president reflects not only the unedifying details of her impeachment but a wider distrust of the political system.

South Korean protesters hold torches during a rally against the president in central Seoul. Photo by Getty Images.

For South Korea’s President Park Geun-hye, the jury is quite literally still out. Impeached by the country’s National Assembly on 9 December over claims of corruption, cronyism and influence peddling, she defiantly rejected – in a detailed statement – all of the charges levelled at her by an independent prosecutor. Any resolution of the issue must now await the ruling of the country’s Constitutional Court on the legitimacy of the impeachment vote – a decision that most likely will come early in the new year.

For the special prosecutor’s office, which is due to start its formal investigation on 21 December, the challenge is to find unambiguous evidence of the president’s direct responsibility for any of the corruption that may have taken place. The president, for her part, can claim, with some credibility that so far she has been tried only in the court of public opinion; that in South Korea’s rumour-prone, scandal-hungry media environment in which prosecutors have been known in the past to leak information to skew public debate, she has been denied natural justice and the presumption of innocence until proven guilty.

Long shadows

But for the more than three-quarters of the Korean public calling for Park’s resignation, the president is symptomatic of Korean society’s wider flaws, including a pattern of corruption, privilege and hypocrisy endemic to the country’s political, economic and social elites. At a time of anemic economic growth (the country’s growth rate is predicted to slow to 2.1% next year), widening wealth and income disparities and reduced employment opportunities for a highly educated workforce, there is a growing mood of populist disaffection with the entire social and political system – for its lack of fairness and transparency and its perceived regulatory inefficiencies. This has been highlighted dramatically by disasters such as the Sewol ferry sinking that claimed the lives of some 300 school-children in August 2014 – at which time the president was castigated for being absent from her office at the time of a grave national crisis.

Complicating the current stand-off is the long-shadow of identity politics and unresolved disagreements about the country’s postwar historical narrative. As the daughter of the man responsible for the Korean economic ‘miracle’ who protected the country from the external communist threat in the North and radical subversion from within, Park’s political lineage is, for the older generation of voters in their sixties and above, a powerful reason to back the beleaguered president.

Already there are signs that this constituency is beginning to rally behind Park, with 30,000 demonstrating on 17 December against the impeachment decision, and with the governing Saenuri party showing signs of a consolidation of power around pro-Park legislators. The president, who has a reputation for stubbornness, may be calculating that this core support may allow her to defy the much larger calls for her resignation. She may also be hoping that the constitutional court, in which the majority of justices are politically conservative, will rule in her favour, allowing her to see out the remainder of her time in office, set to end in February 2018.

A pro-Park ruling by the court seems unlikely given the weight of the circumstantial evidence. Leading opposition politicians, including Moon Jae-in, former head of the Democratic Party and the current front runner in any post-impeachment presidential contest, has warned of a popular ‘revolution’ if the impeachment vote is not upheld. Moreover, the appetite for street protests against the president remains undimmed, and even conservative politicians appear to be positioning themselves for a post-Park era. Ban Ki-moon, the outgoing UN secretary general and long considered a likely Saenuri party candidate for the presidency, has been publicly distancing himself from Park. With 20.5% support, behind Moon on 23.7%, he has compelling reasons to align himself with the popular mood.

Lessons

At an individual level, the experience of President Park combines both political failure and personal tragedy. She has demonstrably failed to live up to her early commitments to represent all Koreans and to bridge the deep divisions between left and right in Korean society. She has also remained deeply isolated from the professional politicians and democratic polity she purports to lead. This is perhaps not so surprising given her authoritarian heritage and the experience of seeing both her parents assassinated in space of five years in the 1970s. The trauma of this experience reportedly made her distrustful of government officials and overly inclined to rely on the guidance of personal friends of dubious reliability, the font of her current troubles. There is also a profound irony that a politician who came to power vowing to place ‘trust-politik’ at the heart of her policy towards North Korea has seen her political position undermined, perhaps fatally, by a near complete collapse in public confidence in her administration.

More widely, the Park saga reveals an important and potentially seismic shift in public attitudes in South Korea, perhaps spurred by a growing populist trend evident elsewhere, whether in the US, Europe or parts of Southeast Asia. Koreans appear to have lost patience with their political system. This new climate of dissent – emboldened by the signs that protest can potentially lead to radical political change – is likely to prove a challenge to any future Korean leader hoping to secure the trust and legitimacy needed to govern.

To comment on this article, please contact Chatham House Feedback




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Biochemical transformation of bacterial lipopolysaccharides by acyloxyacyl hydrolase reduces host injury and promotes recovery [Enzymology]

Animals can sense the presence of microbes in their tissues and mobilize their own defenses by recognizing and responding to conserved microbial structures (often called microbe-associated molecular patterns (MAMPs)). Successful host defenses may kill the invaders, yet the host animal may fail to restore homeostasis if the stimulatory microbial structures are not silenced. Although mice have many mechanisms for limiting their responses to lipopolysaccharide (LPS), a major Gram-negative bacterial MAMP, a highly conserved host lipase is required to extinguish LPS sensing in tissues and restore homeostasis. We review recent progress in understanding how this enzyme, acyloxyacyl hydrolase (AOAH), transforms LPS from stimulus to inhibitor, reduces tissue injury and death from infection, prevents prolonged post-infection immunosuppression, and keeps stimulatory LPS from entering the bloodstream. We also discuss how AOAH may increase sensitivity to pulmonary allergens. Better appreciation of how host enzymes modify LPS and other MAMPs may help prevent tissue injury and hasten recovery from infection.




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Humanin selectively prevents the activation of pro-apoptotic protein BID by sequestering it into fibers [Protein Structure and Folding]

Members of the B-cell lymphoma (BCL-2) protein family regulate mitochondrial outer membrane permeabilization (MOMP), a phenomenon in which mitochondria become porous and release death-propagating complexes during the early stages of apoptosis. Pro-apoptotic BCL-2 proteins oligomerize at the mitochondrial outer membrane during MOMP, inducing pore formation. Of current interest are endogenous factors that can inhibit pro-apoptotic BCL-2 mitochondrial outer membrane translocation and oligomerization. A mitochondrial-derived peptide, Humanin (HN), was reported being expressed from an alternate ORF in the mitochondrial genome and inhibiting apoptosis through interactions with the pro-apoptotic BCL-2 proteins. Specifically, it is known to complex with BAX and BID. We recently reported the fibrillation of HN and BAX into β-sheets. Here, we detail the fibrillation between HN and BID. These fibers were characterized using several spectroscopic techniques, protease fragmentation with mass analysis, and EM. Enhanced fibrillation rates were detected with rising temperatures or pH values and the presence of a detergent. BID fibers are similar to those produced using BAX; however, the structures differ in final conformations of the BCL-2 proteins. BID fibers display both types of secondary structure in the fiber, whereas BAX was converted entirely to β-sheets. The data show that two distinct segments of BID are incorporated into the fiber structure, whereas other portions of BID remain solvent-exposed and retain helical structure. Similar analyses show that anti-apoptotic BCL-xL does not form fibers with humanin. These results support a general mechanism of sequestration of pro-apoptotic BCL-2 proteins into fibers by HN to inhibit MOMP.




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Serum lipoprotein-derived fatty acids regulate hypoxia-inducible factor [Metabolism]

Oxygen regulates hypoxia-inducible factor (HIF) transcription factors to control cell metabolism, erythrogenesis, and angiogenesis. Whereas much has been elucidated about how oxygen regulates HIF, whether lipids affect HIF activity is un-known. Here, using cultured cells and two animal models, we demonstrate that lipoprotein-derived fatty acids are an independent regulator of HIF. Decreasing extracellular lipid supply inhibited HIF prolyl hydroxylation, leading to accumulation of the HIFα subunit of these heterodimeric transcription factors comparable with hypoxia with activation of downstream target genes. The addition of fatty acids to culture medium suppressed this signal, which required an intact mitochondrial respiratory chain. Mechanistically, fatty acids and oxygen are distinct signals integrated to control HIF activity. Finally, we observed lipid signaling to HIF and changes in target gene expression in developing zebrafish and adult mice, and this pathway operates in cancer cells from a range of tissues. This study identifies fatty acids as a physiological modulator of HIF, defining a mechanism for lipoprotein regulation that functions in parallel to oxygen.




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High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site

Alice Santonastaso
Dec 1, 2020; 61:1687-1696
Research Articles




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Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood

Ryunosuke Ohkawa
Dec 1, 2020; 61:1577-1588
Research Articles




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Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice

Aloïs Dusuel
Dec 9, 2020; 0:jlr.RA120000704v1-jlr.RA120000704
Research Articles




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Apolipoprotein C3 and apolipoprotein B colocalize in proximity to macrophages in atherosclerotic lesions in diabetes

Jenny E. Kanter
Dec 8, 2020; 0:jlr.ILR120001217v1-jlr.ILR120001217
Images in Lipid Research




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Distinct patterns of apolipoprotein C-I, C-II and C-III isoforms are associated with markers of Alzheimers disease

Yueming Hu
Dec 11, 2020; 0:jlr.RA120000919v1-jlr.RA120000919
Research Articles




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High-density lipoprotein-associated miRNA is increased following Roux-en-Y gastric bypass surgery for severe obesity [Research Articles]

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affects circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDL were isolated from patients with severe obesity (n=53) before, 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDL were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222 and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222 and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222 and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase (PON1) activity were increased and intracellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with increase in cholesterol efflux capacity (r=0.326, P=0.027 and r=0.349, P=0.017 respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction, and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.




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Apolipoprotein C3 and apolipoprotein B colocalize in proximity to macrophages in atherosclerotic lesions in diabetes [Images in Lipid Research]




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Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice [Research Articles]

Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection.




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Distinct patterns of apolipoprotein C-I, C-II and C-III isoforms are associated with markers of Alzheimers disease [Research Articles]

Apolipoproteins C-I, C-II and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer’s disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1. delineate apoC-I, C-II and C-III isoform profiles in CSF and plasma in a cohort of non-demented older individuals (n = 61), and 2. examine the effect of APOE4 on these isoforms and their correlation with CSF Aβ42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared to matched plasma, with positive correlation between CSF and plasma. A greater percentage of monosialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two non-sialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF, and apoC-II in plasma and CSF, was observed in individuals carrying at least one apoE E4 allele. Increased apoC-I and apoC-II truncations were  associated with lower CSF Aβ42. Finally, monosialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of E4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. These patterns were accentuated in APOE E4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer’s disease pathology with apoCs processing and function in the brain.




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Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a) [Research Articles]

Lipoprotein (a) [Lp(a)] is a risk factor for CVD and a target of therapy, but Lp(a) measurements are not globally standardized. Commercially available assays generally use polyclonal antibodies that detect multiple sites within the kringle (K)IV2 repeat region of Lp(a) and may lead to inaccurate assessments of plasma levels. With increasing awareness of Lp(a) as a cardiovascular risk factor and the active clinical development of new potential therapeutic approaches, the broad availability of reagents capable of providing isoform independence of Lp(a) measurements is paramount. To address this issue, we generated a murine monoclonal antibody that binds to only one site on apo(a). A BALB/C mouse was immunized with a truncated version of apo(a) that contained eight total KIV repeats, including only one copy of KIV2. We generated hybridomas, screened them, and successfully produced a KIV2-independent monoclonal antibody, named LPA-KIV9. Using a variety of truncated apo(a) constructs to map its binding site, we found that LPA-KIV9 binds to KIV9 without binding to plasminogen. Fine peptide mapping revealed that LPA-KIV9 bound to the sequence 4076LETPTVV4082 on KIV9. In conclusion, the generation of monoclonal antibody LPA-KIV9 may be a useful reagent in basic research studies and in the clinical application of Lp(a) measurements.




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Prognostic utility of triglyceride-rich lipoprotein-related markers in patients with coronary artery disease [Research Articles]

TG-rich lipoprotein (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particle-cholesterol (RLP-C), and apoC-III have been associated with atherosclerosis. However, their prognostic values have not been fully determined, especially in patients with previous CAD. This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9–6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C, and apoC-III increased the risk of CVEs by 49% (95% CI: 1.16–1.93), 21% (95% CI: 1.09–1.35), and 40% (95% CI: 1.11–1.77), respectively. High TRL-C, RLP-C, and apoC-III were also independent predictors of CVEs in individuals with LDL-C levels ≤1.8 mmol/l (n = 1,068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination, and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.




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ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPLs hydrolase domain [Images In Lipid Research]




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The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase [Research Articles]

For three decades, the LPL–specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.




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Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation [Research Articles]

Lipoprotein (a) [Lp(a)] is a well-known risk factor for cardiovascular disease, but analysis on Lp(a) and renal dysfunction is scarce. We aimed to investigate prospectively the association of serum Lp(a) with the risk of reduced renal function, and further investigated whether diabetic or hypertensive status modified such association. Six thousand two hundred and fifty-seven Chinese adults aged ≤40 years and free of reduced renal function at baseline were included in the study. Reduced renal function was defined as estimated glomerular filtration rate <60 ml/min/1.73 m2. During a mean follow-up of 4.4 years, 158 participants developed reduced renal function. Each one-unit increase in log10-Lp(a) (milligrams per deciliter) was associated with a 1.99-fold (95% CI 1.15–3.43) increased risk of incident reduced renal function; the multivariable-adjusted odds ratio (OR) for the highest tertile of Lp(a) was 1.61 (95% CI 1.03–2.52) compared with the lowest tertile (P for trend = 0.03). The stratified analysis showed the association of serum Lp(a) and incident reduced renal function was more prominent in participants with prevalent diabetes [OR 4.04, 95% CI (1.42–11.54)] or hypertension [OR 2.18, 95% CI (1.22–3.89)]. A stronger association was observed in the group with diabetes and high Lp(a) (>25 mg/dl), indicating a combined effect of diabetes and high Lp(a) on the reduced renal function risk. An elevated Lp(a) level was independently associated with risk of incident reduced renal function, especially in diabetic or hypertensive patients.




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Genetic susceptibility, dietary cholesterol intake, and plasma cholesterol levels in a Chinese population [Patient-Oriented and Epidemiological Research]

Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRSTC, 57 SNPs), LDL-C (GRSLDL-C, 45 SNPs), and HDL-C (GRSHDL-C, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRSTC (effect sizes: –0.29, 0.34, 2.45, and 6.47; Pinteraction = 0.002) and GRSLDL-C (effect sizes: –1.35, 0.17, 5.45, and 6.07; Pinteraction = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRSTC (Pinteraction = 0.001) and GRSLDL-C (Pinteraction = 0.004). The adverse effects of GRSTC on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; Pinteraction = 0.023) and GRSLDL-C on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; Pinteraction = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.




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Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice [Research Articles]

Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of 18F-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with β-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP1-mediated thermogenesis. In metabolic studies using radiolabeled tracers, we found that glucose uptake is increased in mildly cold-activated BAT of Ucp1–/– versus WT mice kept at subthermoneutral temperature. Conversely, lower glucose disposal was detected after full thermogenic activation achieved by sustained cold exposure or CL treatment. In contrast, uptake of lipoprotein-derived fatty acids into chronically activated thermogenic adipose tissues was substantially increased in UCP1-deficient mice. This effect is linked to higher sympathetic tone in adipose tissues of Ucp1–/– mice, as indicated by elevated levels of thermogenic genes in BAT and WAT. Thus, glucose and lipoprotein handling does not necessarily reflect UCP1-dependent thermogenic activity, but especially lipid uptake rather mirrors sympathetic activation of adipose tissues.




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High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site [Research Articles]

Lipoprotein (a) [Lp(a)] is characterized by an LDL-like composition in terms of lipids and apoB100, and by one copy of a unique glycoprotein, apo(a). The apo(a) structure is mainly based on the repetition of tandem kringle domains with high homology to plasminogen kringles 4 and 5. Among them, kringle IV type 2 (KIV-2) is present in a highly variable number of genetically encoded repeats, whose length is inversely related to Lp(a) plasma concentration and cardiovascular risk. Despite it being the major component of apo(a), the actual function of KIV-2 is still unclear. Here, we describe the first high-resolution crystallographic structure of this domain. It shows a general fold very similar to other KIV domains with high and intermediate affinity for the lysine analog, -aminocaproic acid. Interestingly, KIV-2 presents a lysine binding site (LBS) with a unique shape and charge distribution. KIV-2 affinity for predicted small molecule binders was found to be negligible in surface plasmon resonance experiments; and with the LBS being nonfunctional, we propose to rename it "pseudo-LBS". Further investigation of the protein by computational small-molecule docking allowed us to identify a possible heparin-binding site away from the LBS, which was confirmed by specific reverse charge mutations abolishing heparin binding. This study opens new possibilities to define the pathogenesis of Lp(a)-related diseases and to facilitate the design of specific therapeutic drugs.




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Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood [Research Articles]

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1+/+ and Abca1–/– mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.




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WITHDRAWN: Extraordinary apolipoprotein oxidation in chronic hepatitis C and liver cirrhosis [13. Other]

Withdrawn by Author.




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Exploring Transatlantic Responses to Far-right Populism in Europe: Simulation Exercise

Exploring Transatlantic Responses to Far-right Populism in Europe: Simulation Exercise Research paper sysadmin 1 May 2018

A new paper summarizes the findings of a recent simulation exercise exploring how governments on both sides of the Atlantic might respond to a descent towards populist authoritarianism in an EU member state.

Young protester, Serbia. Photo: urbazon/Getty Images.

Summary

  • To better understand how governments on both sides of the Atlantic might respond to a descent towards populist authoritarianism in an EU member state, Chatham House organized a simulation event involving a group of experts drawn from the public sector, academia and NGOs.
  • Simulation exercises enable the testing and modelling of the responses of different actors when presented with specific situations; participants’ interactions in a given set of circumstances are explored, and patterns of negotiation are captured and analysed.
  • In this simulation, European, US and multilateral representatives were given the task of managing relations with Baltia, a fictional Eastern European state on the verge of electing a far-right nationalist, Eurosceptic government. They were then challenged to manage their relationship with Baltia after it had elected such a government, which was pushing for a ‘leave’ vote in a planned referendum on the country’s continued EU membership.
  • The simulation highlighted a number of issues:
    • Limited instruments are available to liberal democratic governments where there is cause for concern regarding the outcome of an election in an allied country. There are relatively few tools at the disposal of governments to support political allies, or to prevent outcomes that are perceived as threatening democratic norms. The simulation reinforced the view that interventionist moves, either from the European Commission or from individual national governments, would be more likely to come in response to an unfavourable development rather than pre-emptively.
    • The EU, and caucuses of European states, are the main international interlocutors in this type of political crisis involving an EU member state. The US opted to play a limited role in the negotiations; the same was largely true for NATO, aside from its action in sharing intelligence about a potential coup in Baltia. France and Germany formed a natural working partnership, taking meetings together and coordinating policies first before discussing them with a wider European circle, although their positions did not always align.
    • The UK’s capacity to shape the outcome of collective EU discussions appeared more restricted, while Brexit also seemed to shape the response of other EU states to the developing situation in Baltia. Although member states were undoubtedly reluctant to see another country go down this route, they were also resolute in demonstrating a unity of approach and limited flexibility in the face of the new populist government’s attempt to divide them.




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Hope, Peace and Reconciliation: Pope Francis in Mozambique

Hope, Peace and Reconciliation: Pope Francis in Mozambique Expert comment sysadmin 4 September 2019

A papal visit will highlight the importance of the recently signed peace agreement between the government and opposition.

Sales of papal-pictured capulanas have been brisk. Photo: Chatham House.

Pope Francis’ visit to Mozambique on 4–6 September comes at a critical political moment. The theme for the papal Africa trip (which also includes Madagascar and Mauritius) is ‘pilgrim of hope, peace and reconciliation’. This is especially relevant for Mozambique, as this is the first week of the official campaign for Mozambique’s sixth national elections on 15 October.

It is also the one-month anniversary of the Maputo Accords for Peace and Reconciliation between the government and the armed opposition, RENAMO (and the fifth anniversary of the previous such agreement in 2014).

What is unusual is that the pope accepted to visit Mozambique just after a peace accord and in the run-up to national elections. Something similar has happened only once, when Pope John Paul II visited Angola in June 1992 (following the Bicesse Accords) prior to the country’s first ever national elections in September. Unfortunately Pope John Paul’s preaching of reconciliation and pluralism failed and civil war resumed some months later, following rejection of the preliminary election results. Angola’s civil war only finally ended a decade later in 2002.

The last papal visit to Mozambique was also by Pope John Paul II in 1988, when civil war was still ongoing, and the country was still a single party state. Despite the war, massive congregations attended and RENAMO reached local ceasefires and agreements to maintain electricity supply to honour the visit. Some of the seeds for the Rome peace process were laid during this trip – especially as it also represented a formal reconciliation of FRELIMO, the ruling party, with the Catholic Church.

This papal visit to Mozambique is equally anticipated, as was highlighted several times during speeches at the 6 August peace agreement signing in Maputo. When I was in Maputo last month, sales of papal-pictured capulanas (a Mozambican sarong) were brisk and Mozambican television carried countdown clocks on many programmes for the touchdown of Pope Francis on national soil.

The Catholic Church has played an instrumental role in promoting peace in Mozambique over the years. The 1977–92 civil war ended through negotiations hosted at the Sant’ Egidio lay community in Rome, and the current Archbishop of Bologna, Dom Matteo Zuppi (who led the Sant’ Egido negotiations in 1992 and is soon to be made a cardinal) was an official witness to 6 August accords signing.

When targeted armed conflict resumed in 2013, faith groups once more re-engaged and in 2016 Sant’ Egidio once more co-led mediation efforts, less successfully than in 1991–92. Sant’ Egidio (including during a presidential visit to Rome in July) contributed to convincing the Vatican that this papal visit should occur before the October elections.

President Filipe Nyusi anxiously wanted this visit to occur before the elections. He is seeking re-election for his second and final term and a papal visit should help win some votes. His party, FRELIMO, is also worried about securing a majority in the national assembly, as it has been weakened by patchy delivery of services and ongoing high-level corruption scandals.

This year, President Nyusi’s priorities have been to show that he can attract international investment (such as Andarko’s recently announced final investment decision on its gas project), a peace agreement with RENAMO (the August agreements) and a papal visit, so a successful trip would complete his goals.

The pope’s ‘hope, peace and reconciliation’ message of his visit is important. Twice previously, the FRELIMO-led government and RENAMO have reached definitive agreements, in Rome (1992) and Maputo (2014), but failed to fully end bloodshed. This new August 2019 agreement is the third attempt, and if it is to last, it will require political goodwill, compromise and an acceptance of more inclusive national politics by both parties.

There are two immediate threats to this agreement. The first is the forthcoming 15 October elections and their conduct could make or break it. Accepting reconciliation and greater pluralism underpins this agreement, but RENAMO expects to increase its share of the parliamentary vote and win a majority in some provinces (and therefore indirectly elect their choice for governor).

A second threat is the ‘Military Junta’, a RENAMO splinter group that claims to be 500 strong, but probably accounts for 80 armed persons. It rejects the 6 August agreement and warns that it could disrupt the elections. This group has asked for mediation, and hopefully can be accommodated in a side deal to the main one agreed in August, which already provides for the reintegration of over 5,000 RENAMO supporters and combatants.

A recent Chatham House research paper on elite bargains in Mozambique concluded that the October elections will be the first immediate test of the August agreement. If the elections pass without significant electoral manipulation or violence and this August deal sticks on the third attempt, the domestic focus should then move onto poverty reduction, combating inequality, education and solving the new security crisis with Islamic militants in Cabo Delgado province.




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Culture notes: Populists of the world unite

Culture notes: Populists of the world unite The World Today rsoppelsa.drupal 25 May 2022

America’s hard-right has successfully played a long game at home, and now it’s schmoozing Europe. We should be worried, says Catherine Fieschi

The politics of advanced democracies is a rather Janus-faced affair these days. No sooner have we breathed a sigh of relief at the results of the French presidential election than a leaked United States Supreme Court document on Roe v Wade signals American abortion rights are under threat. 

Yes, Europe seems to be maintaining political unity in its support of Ukraine, and the US is lavishing eye-watering sums on it both in military and humanitarian aid. Yet one cannot help but feel that these might be short-lived spells of relief in the face of mounting storm clouds on the political horizon. Both at the domestic and international level, populist politics looks to be gathering pace still. 

On the domestic front, we should be cautious in our relief. In the French elections Emmanuel Macron was indeed re-elected, and comfortably so, but there is no denying the space occupied by populist politicians on the left and the right. In the first round, Marine Le Pen gained 23 per cent of the vote, left populist candidate Jean-Luc Mélenchon 22 per cent, and far-right candidate Éric Zemmour 7 per cent. Add to this a record low turnout, and the picture is one of a system in which mainstream politics has overall been rejected in favour of various populist options. 

The Hungarians weren’t so lucky, and Viktor Orbán’s capture of the media and quashing of the opposition over his years in power delivered solid victory. 

What should be cause for further concern is what is happening in the United States, as well as its potential impact on European politics. A quick flick through American politics today suggests dysfunctionalities of staggering magnitude and depth, and the full extent of the success of the right-wing Republican project, as confirmed by the intention to reverse Roe v Wade. 

Any reversal of Roe v Wade is a further step towards a drastic re-territorialization of American politics: into red states and blue states, into urban v rural, into places where taxes fund public education and public goods and where they won’t. It is also about a re-territorialization of institutional power away from the federal and into state institutions. 

The words of JD Vance, the Ohio Republican senatorial candidate – author of the rather good memoir Hillbilly Elegy – pander to an ‘American heartlands’ view of the United States’ role in the world. Asked about the fate of Ukraine, Vance simply replied that he ‘didn’t really care what happens to Ukraine one way or another’. 

On an even more basic level, we would do well to keep in mind that there were 440 anti-voter bills in 49 states at the end of 2021 and rising, calling into question citizens’ basic rights to vote. Republicans have pursued this agenda relentlessly. They have played a long game and invested in media, education and minor and not so minor projects – all of which have secured them a social and political base that is well-disposed towards the deep reversal of the American liberal global project and that of its allies across the world.

The arrival of the Fox News-driven Conservative Political Action Conference in Hungary in May is deeply worrying

And it is perhaps on this last point that we should be most alarmed. Between May 18-20, the Conservative Political Action Conference, an American conclave of the right, was held in Europe. Viktor Orbán gave the keynote speech, and other speakers included the Brazilian President Jair Bolsonaro’s son, Eduardo, and the president of Spain’s far-right party Vox, Santiago Abascal, as well as some well-known American Trumpian voices, including Trump himself. Marine Le Pen, whose earlier appearance at the conference had met with rapturous applause, chose not to cosy-up too closely to Orbán in the run-up to the French parliamentary elections in June but she sent her deputy. 

The export of the Fox News-driven conference from across the Atlantic is deeply worrying. Up until now populists have failed in their attempts at international alliances. At the European Union level their nationalism has always been in the way of their working together, and their groups tend to be short-lived or ineffective as a result. As for American attempts in Europe, the one led by Steve Bannon, the former White House adviser, in 2020 that aimed to create an Academy for the Judeo-Christian West ended as a damp squib – possibly not helped by his dismissal from the White House amid charges of defrauding donors.

But something may be changing: the conference’s embrace of Orbán and an international smattering of ‘strongmen’ hailing from the hard-right, aligned with Putin and sup-ported by Trump and a media empire, suggests that we are entering a Trumpian-infused second act that in its triumphal revanchism is seeking to create an international right-wing populist, or even authoritarian front. This is about politics, media, but also money – something European populist parties have been short of. As Marine Le Pen explained to French voters, her party is so poor it had to borrow money from a Russian bank.  

As some have pointed out, the Russian aggression against Ukraine has complicated matters when it comes to Russian funding of disinformation to the West. Many routes have been shut down. But a new route between the US and Hungary as a platform to floss Europe with dirty money is a good replacement to the old Russian route. 
 




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Gorbachev's complex legacy is beyond the popular belief

Gorbachev's complex legacy is beyond the popular belief Expert comment NCapeling 3 September 2022

The last major figure with a decisive Cold War role, Mikhail Gorbachev was not as bad as Putin’s Russia portrays him, but also not as heroic as the West thinks.

Arguably the worst year of the Cold War since the Cuban Missile Crisis was 1983, with three major incidents which escalated East-West tensions – and any one of them could have led to a full-scale war.

The first was the Korean Airline KAL007 being shot down by an SU15 fighter aircraft for straying into Soviet airspace, killing all 269 passengers and crew. Then came the identification of signals from Soviet satellites as being incoming US intercontinental ballistic missiles – Colonel Stanislav Petrov, going against all protocols, thankfully decided to report them as a false alarm before he could be sure.

The third was perhaps the most dangerous, being the misinterpretation of a live-fire NATO exercise which was believed by some in both East Germany and Russia to be a front for an imminent attack.

The greatest disappointment in Gorbachev’s legacy was he completely believed the USSR could be reformed and still survive as an entity while others, such as Boris Yeltsin and Ronald Reagan, understood it had to be dismantled

All three incidents occurred in the few months following the infamous March 1983 ‘Star Wars’ speech by US president Ronald Reagan, in which he talked about nuclear arms control and laid out the US case for a ballistic missile defence programme.

At that time Mikhail Sergeyevich Gorbachev was the youngest serving member of the USSR Politburo, known to be a favourite of Soviet leader Yuri Andropov, and it is highly likely he had been aware of these close calls and was part of discussions within Kremlin decision-making circles.

A changemaker both inside and outside the USSR

Following the deaths of Andropov in 1984 and his replacement Konstantin Chernenko in 1985, Gorbachev’s appointment as general secretary of the Communist Party saw him immediately begin to change the Soviet Union from within – and also change relationships with the major Western powers, especially the US, Germany, and the UK.

His policies of glasnost (openness) and perestroika (restructuring) were primarily aimed at internal reforms but translated into a major reset of international relations and international security. During his six years as leader, Gorbachev initiated many arms control negotiations which resulted in treaties and increased both the transparency and the confidence between the USSR and the US.

These included the 1986 Stockholm Accord which emanated from the Helsinki Process and allowed for the observation and inspection of large-scale military exercises, the 1985 resumption of the Strategic Arms Reduction Talks which lead to START I, and the 1987 INF Treaty in which the USSR ‘out-yessed’ the US – the most open and transparent disarmament treaty in terms of notification and verification measures ever agreed.

There was also a reciprocal moratorium on nuclear weapons tests starting from 1985 – which laid the groundwork for the 1996 CTBT – the 1991 Chemical Weapons Convention, and the 1990 Conventional Forces in Europe (CFE) Treaty.

The most dramatic moment of all was when Gorbachev and Reagan met at a summit in Reykjavik and came close to deciding to eliminate nuclear weapons – but the initiative failed to reach agreement, mainly because Reagan could not drop his commitment to ballistic missile defences and Gorbachev could not accept the offer of joint development.

Nonetheless, all these nuclear arms control treaties led the way for their descendants which have kept nuclear weapons in check ever since and are still in place in the form of the New START agreement.

During his six years as leader, Gorbachev initiated many arms control negotiations which resulted in treaties and increased both the transparency and the confidence between the USSR and the US

But despite these outstanding achievements, Gorbachev had blind spots – such as enabling rather than destroying the USSR bioweapons programme, unlike the US which had dismantled its own bioweapons offensive capability by 1973.

And it is now known that, despite negotiating the Chemical Weapons Convention, Russia withheld information on new chemical weapons agents – Novichoks – which have since been used to lethal effect by Russia in Salisbury and against figures opposing the current regime.

His misguided faith in a Soviet future

Gorbachev was markedly different to his predecessors as secretary general. He was neither as decrepit nor as hardline, and he understood from the outset that the Soviet Union was, by the 1980s, finally dying.

Using the intellectual abilities of Aleksandr Yakovlev, he forced through the reforms which simultaneously captured the imagination of the free world and liberated his countrymen and women.

But although he built solid relationships – even friendships – with the world’s major heads of state and improved the USSR’s human rights, releasing dissidents such as Andrei Sakharov, but many – especially Ukrainian dissidents – continued to languish in camps.

The greatest disappointment in Gorbachev’s legacy was he completely believed the USSR could be reformed and still survive as an entity while others, such as Boris Yeltsin and Ronald Reagan, understood it had to be dismantled.

This shortcoming is especially uncomfortable as today’s Russia continues to insist it has a given right to control other former Soviet states, to the extent it is willing to destroy them if they do not concede.




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Eurovision, war and the geopolitics of pop

Eurovision, war and the geopolitics of pop The World Today mhiggins.drupal 28 March 2023

Europe’s great song competition may strive for continental harmony, but bitter conflicts and voting blocs often drag it off key, writes Saskia Postema.

In May, the city that spawned the Beatles will add another notch to its cultural belt as Liverpool hosts the Eurovision Song Contest.

The pop competition has been celebrating extravagance, dramatic acts and lots of glitter since 1956. It is expressly designed to be non-political, with performers barred from promoting political interests, yet it exists for a specific political purpose – to promote European unity.

The organizer, the European Broadcasting Union (EBU), has certainly succeeded in part with its mission. While Europe Day on May 9 comes and goes without much fanfare, Eurovision is an eagerly anticipated fixture on the cultural calendar.

Cultural diplomacy

While some may dismiss it as simply an extravagant party, there is more to it than that: it is a form of cultural diplomacy. Beyond artistry, acts are expected to bring their cultural identity to the stage as they bid for douze points, Eurovision’s highest score, from national juries.

Like any popular forum, it reflects popular opinion. So, when war threatens the European harmony Eurovision is meant to exude, politics inevitably manifests itself.

This was evident last year. Following Russia’s invasion of Ukraine in February, Eurovision’s organizers reiterated their apolitical stance stating both countries would be allowed to participate. But when various countries threatened to withdraw if Russia was allowed to compete, the EBU changed its tune and broke off ties with Russian broadcasting agencies indefinitely. As reluctant as it was to act in this capacity, the organization still inadvertently highlighted its role as a political gatekeeper and confirmed Eurovision does function as a political arena.

The first ‘nul points’ awarded to the UK in 2003 was seen as a backlash against the Iraq war

Unsurprisingly, all eyes were on the Ukrainian entry that year. Kalush Orchestra’s Stefania, presenting a blend of traditional Ukrainian folk music with hip hop beats, went on to win the contest resoundingly.

And while the winning nation normally hosts next year’s competition, due to the war this honour passed to the runner-up, the United Kingdom. Britain, coincidentally, has been one of the most visible supporters of Kyiv’s war efforts. Boris Johnson, the former prime minister, was among the first leaders to visit Kyiv after the Russian invasion.

Last year’s second place ended a long spate of poor results for the UK in the competition. The first year it scored nul points was 2003 when the UK entry was Cry Baby by the duo Jemini. The result was seen widely as a backlash against Britain’s entry into the Iraq war earlier that year.

In the intervening years it has been placed last twice and received nul points again in 2021 when the entry was Embers sung by James Newman. With last year’s second place for Sam Ryder’s Space Man, the UK redeemed itself and will get to host Eurovision in Liverpool, a city twinned with Odesa since 1957.

It is not the first time that Russia’s geopolitical relations have led to Eurovision controversy. In 2008, following the Russo-Georgian war, Russia recognized the self-proclaimed independence of South Ossetia and Abkhazia which had broken away from Georgia.

Despite Russian objections, Ukraine’s 2016 entry about Stalin’s deportation of Crimean Tatars was permitted – and won

As a result, Georgia initially refused to take part in the 2009 Eurovision as it was to be held in Moscow. It changed its mind, however, submitting a song by Stefane and 3G called We Don’t Wanna Put In. The submission was rejected by the EBU, which said it contained obvious references to the Russian leader, something Georgia denied.

In 2015, Ukraine withdrew from Eurovision following the Russian annexation of Crimea. The following year the EBU was faced with a similar problem when Ukraine submitted a song, 1944,sung by Jamala, which told the story of her great-grandmother who lived through the mass deportation of Crimean Tatars in the Soviet Union under Josef Stalin. This time the EBU allowed the entry, despite the Russian Duma calling for its rejection. The song went on to win.

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A year after Russia annexed Crimea, Ukraine’s triumphant 2016 Eurovision entry, ‘1944’ by Jamala, touched on the mass deportation of Crimean Tatars in the Soviet Union.

Country-level voting behaviour, in general, can reveal interesting trends, starting with neighbourly support. Geographical voting blocs are a reality – whether it is Belgium and the Netherlands awarding each other points, the former Soviet Bloc countries showing preference for one another, or the Nordic states exchanging highest scores.

In 2004 hosts Turkey refused to screen a map of the Republic of Cyprus

Similarly, voting trends might be indicative of large diaspora communities living in a particular country. They can also provide insights into political trends. Amid rising tensions between Armenia and Azerbaijan in 2009, police reportedly questioned all 43 Azerbaijan judges who had voted for Armenia, resulting in a fine from the EBU.

On the flipside, when Istanbul hosted the 2004 contest, it marked the first time that Turkey and Cyprus recognized each other through voting despite ongoing tensions, although Turkey still refused to screen a map of the Republic of Cyprus, which it does not recognize, when that country’s votes were announced as is custom.

Participation means recognition 

Indeed, participation means recognition for countries. It shows kinship to the European continent, particularly attractive in the early 2000s during the initial waves of accession to the European Union by Eastern Bloc countries.

Participation also offers individual recognition for the acts, whose mere involvement may promote diversity and inclusion. Having achieved a cult following from the LGBT community, Eurovision has become a platform for the promotion of human rights as well, exemplified by Austria’s 2014 winner Rise Like a Phoenix by Conchita Wurst, a moustachioed drag performer in a ball gown.

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The drag performer Conchita Wurst won Eurovision for Austria in 2014 with ‘Rise Like a Phoenix’.

Eurovision acts as a gauge for cultural trends across the continent. As a result, it simply cannot be apolitical, not when countries such as Hungary withdraw from the competition calling Eurovision ‘too gay’. Interestingly, when China censored Ireland’s 2018 entry because it included two men dancing together, the EBU chose not to break ties.




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Populous suburban Philly county orders schools to go remote




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Populous suburban Philly county orders schools to go remote




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Where They Are: The Nation's Small But Growing Population of Black English-Learners

In five northern U.S. states, black students comprise more than a fifth of ELL enrollment.




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Where They Are: The Nation's Small But Growing Population of Black English-Learners

In five northern U.S. states, black students comprise more than a fifth of ELL enrollment.




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Sequential Activation of Lateral Hypothalamic Neuronal Populations during Feeding and Their Assembly by Gamma Oscillations

Mahsa Altafi
Oct 23, 2024; 44:e0518242024-e0518242024
Systems/Circuits




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Pop-up craft

Have fun with pop-up craft activities in the Objects Gallery 




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Targeting Cre Recombinase to Specific Neuron Populations with Bacterial Artificial Chromosome Constructs

Shiaoching Gong
Sep 12, 2007; 27:9817-9823
Toolbox




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Sequential Activation of Lateral Hypothalamic Neuronal Populations during Feeding and Their Assembly by Gamma Oscillations

Neural circuits supporting innate behaviors, such as feeding, exploration, and social interaction, intermingle in the lateral hypothalamus (LH). Although previous studies have shown that individual LH neurons change their firing relative to the baseline during one or more behaviors, the firing rate dynamics of LH populations within behavioral episodes and the coordination of behavior-related LH populations remain largely unknown. Here, using unsupervised graph-based clustering of LH neurons firing rate dynamics in freely behaving male mice, we identified distinct populations of cells whose activity corresponds to feeding, specific times during feeding bouts, or other innate behaviors—social interaction and novel object exploration. Feeding-related cells fired together with a higher probability during slow and fast gamma oscillations (30–60 and 60–90 Hz) than during nonrhythmic epochs. In contrast, the cofiring of neurons signaling other behaviors than feeding was overall similar between slow gamma and nonrhythmic epochs but increased during fast gamma oscillations. These results reveal a neural organization of ethological hierarchies in the LH and point to behavior-specific motivational systems, the dysfunction of which may contribute to mental disorders.




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Pope Francis to attend the Second International Conference on Nutrition (ICN2)

Pope Francis will add his voice to the fight against hunger and malnutrition by addressing the Second International [...]




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This World Food Day, Pope Francis addresses FAO and the international community

World Food Day is coming up this Monday, October 16. This year’s theme, Change the future of migration. Invest in food security and rural development, highlights FAO’s work in [...]




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Indiana's Secret Parties and Perfect Popcorn

A large portion of Indiana's economy relies on an invaluable crop: corn. Popcorn plants like Pop Weaver have perfected the production of our favorite movie snack down to a science.




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Assessing Coral Populations

Marine biologist Nancy Knowlton discusses a research trip to the Smithsonian Tropical Research Institute, in Panama, where she and her collaborators collected data on coral reef populations. Reef sustainability is closely tied to coral reproduction. Then director of the Center for Marine Biodiversity and Conservation at the Scripps Institution of Oceanography, Knowlton, who has since been hired to lead the Smithsonian's Ocean Initiative, has reservations about the long-term future of corals




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Thiebaud on Being a Pop Artist

The artist discusses where his work fits among the many genres of painting




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Easter Island's Ancient Population Never Faced Ecological Collapse, Suggests Another Study

New DNA analysis adds to growing research indicating the famous Pacific island did not collapse from overuse of resources before the arrival of Europeans




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Visualization of Apoptotic Ovarian Follicles during Aedes aegypti Mosquito Egg Maturation by Fluorescent Imaging Studies

In insects, oocyte resorption (oosorption) or follicular atresia is one of the key physiological processes and evolutionary strategies used to optimize reproductive fitness. Mosquitoes are ideal model organisms for studying egg maturation in arthropods, as their follicle development is initiated only following the ingestion of a blood meal, followed by a carefully orchestrated series of hormonally regulated events leading to egg maturation. A cohort of approximately 100 follicles per mosquito ovary begin developing synchronously. However, a significant fraction of follicles ultimately undergo apoptosis and oosorption, especially when available resources from the blood meal are limited. Therefore, simple, rapid, and reliable techniques to accurately evaluate follicular atresia are necessary to understand mechanisms underlying follicle development in insects. This protocol describes how to detect apoptotic follicle cells within the Aedes aegypti mosquito ovaries using a commercially available fluorescent-labeled inhibitor of caspases (FLICA). Caspases are key players in animal apoptosis. In this assay, the FLICA reagent enters the intracellular compartment of follicles in dissected mosquito ovaries and covalently binds to active caspases. The bound reagent remains within the cell and its fluorescent signal can be observed by confocal microscopy. Although this method was specifically developed for visualizing apoptotic ovarian follicles during Ae. aegypti mosquito egg development, it should be applicable to other mosquito tissues that undergo caspase-mediated program cell death in a time-dependent manner.




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Weekend fire damages popular Saint Andrews eatery, the Herring

Emergency officials said the fire at the Herring Pub and Restaurant on Water Street broke out around 4 p.m. and appears to have started in an air conditioning unit.   



  • News/Canada/New Brunswick