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Recycler, property sector subsidies set

The Government today said the first batch of subsidies amounting to $5.6 million under two relief measures for recyclers has been disbursed, while $5.6 million in subsidies had been approved under a management sector support scheme.

 

The two Recycling Fund measures aim to help the recycling industry cope with the current economic situation and recent operational difficulties arising from the COVID-19 epidemic.

 

The Advisory Committee on Recycling Fund announced in mid-March to reserve $100 million to launch the One-off Recycling Industry Anti-epidemic Scheme.

 

The scheme provides timely financial support to help with recyclers’ operational costs for six months. The funding limit for each recycler is $20,000 per month from January 1 to June 30, or $120,000 in total maximum subsidy.

 

The committee has also allocated additional funds to extend the earlier-launched One-off Rental Support Scheme for another six months, providing a total funding of $200 million to fight the virus and help the recycling industry ride out the difficult times.

 

The rental support scheme, which benefits street-corner recycling shops and recycling sites, originally ran from October to March. It has been extended for six months until September this year, totalling 12 months.

 

The monthly rental subsidy for each recycler is capped at $25,000, setting the maximum total rental subsidy at $300,000.

 

Separately, the Anti-epidemic Support Scheme for Property Management Sector has approved 205 applications involving around $5.6 million in subsidies to benefit more than 1,500 building blocks.

 

The relevant property management companies and owners’ organisations will receive notifications for subsidy disbursement shortly.

 

The list of properties for which applications have been approved is available online.

 

Briefing sessions were held earlier to introduce the scheme to the property management sector and owners’ organisations.




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Carbohydrate Content in the GDM Diet: Two Views: View 1: Nutrition Therapy in Gestational Diabetes: The Case for Complex Carbohydrates

Teri L. Hernandez
May 1, 2016; 29:82-88
From Research to Practice




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People just wah hear sumpn different - Govana finds captive audience as ‘Convo Pt 2’ hits a million views

Back in January when dancehall artiste Govana released the track HAMANTS Convo, the storyline captivated listeners across the globe. For weeks, the song, which highlights infidelity in relationships, trended at number one on the local YouTube...




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J’can healthcare worker dies from COVID-19-related complications

Antoniette Bryden has fond memories of her mother, Arlene Reid, 51, a healthcare worker originally from Yallahs, St Thomas, who died of COVID-19 in Brampton, Ontario, Canada, on April 27. Reid, a personal support worker (PSW) who worked part-time...




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A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

Dorte B. Bekker-Jensen
Apr 1, 2020; 19:716-729
Technological Innovation and Resources




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Initial studies with [11C]vorozole positron emission tomography detect over-expression of intra-tumoral aromatase in breast cancer

Introduction: Aromatase inhibitors are the mainstay of hormonal therapy in estrogen receptor positive, postmenopausal breast cancer, although response rate is just over 50%. The goal of the present study was to validate and optimize positron emission tomography (PET) with 11C-vorozole for measuring aromatase expression in postmenopausal breast cancer. Methods: Ten newly diagnosed, postmenopausal women with biopsy confirmed breast cancer were administered 11C-vorozole intravenously and PET emission data collected between 40 – 90 minutes post-injection. Tracer injection and scanning were repeated 2 hours after ingestion of 2.5mg letrozole p.o. Mean and maximal standard uptake values and ratios to non-tumor tissue (SUVs, SUVRs) were calculated for tumor and non-tumor regions at baseline and after letrozole. Biopsy specimens from the same tumors were stained for aromatase using immunohistochemistry and evaluated for stain intensity and the percentage of immune-positive cells. Results: Seven of the 10 women (70%) demonstrated increased focal uptake of tracer (SUVR>1.1) coinciding with the mammographic location of the lesion. The other 3 women (30%) did not show increased uptake in the tumor (SUVR <1.0). All of the cases with SUVR above 1.1 had SUVs above 2.4 and there was no overlap in SUV between the two groups, with mean SUV in tumors overexpressing aromatase (SUVR>1.1) ranging from 2.47 to 13.6, while tumors not overexpressing aromatase (SUVR<1) ranged from 0.8 to 1.8. Pretreatment with letrozole reduced tracer uptake in the majority of subjects; although the %blocking varied across and within tumors. Tumors with high SUV in vivo also showed high staining intensity on IHC. Conclusion: PET with 11C-vorozole is a useful technique for measuring aromatase expression in individual breast lesions, enabling a non-invasive quantitative measurement of baseline and post-treatment aromatase availability in primary tumors and metastatic lesions.




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11C-PABA as a Novel PET Radiotracer for Functional Renal Imaging: Preclinical and First-in-Human Studies

para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-hour urine sampling. Therefore, we hypothesized that radiolabeled PABA with 11C could allow high-quality dynamic PET of the kidneys while reducing the radiation exposure due to its short biological and physical half-lives. We evaluated if 11C-PABA could visualize renal anatomy and quantify function in healthy rats, rabbits, and first-in-human studies in healthy volunteers. Methods: Healthy rats and rabbits were injected with 11C-PABA intravenously. Subsequently, a dynamic PET was performed, followed by post-mortem tissue biodistribution studies. 11C-PABA PET was directly compared with the current standard, 99mTc-MAG3 in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of 11C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of 11C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, 11C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then renal pelvis with high spatiotemporal resolution. Conclusion: 11C-PABA demonstrated fast renal excretion with very low background signal in animals and humans. These results suggest that 11C-PABA could be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.




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PET imaging of phosphodiesterase-4 identifies affected dysplastic bone in McCune-Albright syndrome, a genetic mosaic disorder

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3', 5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gsα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of Gsα in the affected tissues. The Gsα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS, but not in humans with fibrous dysplasia. Positron emission tomography (PET) imaging of PDE4 with 11C-(R)-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods: 11C-(R)-rolipram whole-body and brain PET scans were performed in six individuals with MAS (three for brain scans and six for whole-body scans) and nine healthy controls (seven for brain scans and six for whole-body scans). Results: 11C-(R)-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in 11C-(R)-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected, which could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with 11C-(R)-rolipram to indirectly measure increased cAMP pathway activation in human disease.




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Reported differences between Digital and Analog PET/CT studies




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Secrecy, spies and the global South: intelligence studies beyond the 'Five Eyes' alliance

6 November 2019 , Volume 95, Number 6

Zakia Shiraz and Richard J. Aldrich

The study of secrecy and spies remain subjects dominated by Anglo-American experiences. In recent years there has been some effort to refocus the lens of research upon ‘intelligence elsewhere’, including the global South. This is partly because of intense interest in the Arab Spring and ‘managed democracy’, placing a wider range of secret services under the spotlight. However, the approach to research is still dominated by concepts and methods derived from studying the English-speaking states of the ‘Five Eyes’ alliance and their European outriders. This article calls for a re-examination of research strategies for Intelligence Studies and for those theorizing surveillance, suggesting that both fields have much to learn from area studies and development studies, especially in the realm of research practice and ethics. If the growing number of academics specializing in intelligence genuinely wish to move forward and examine the global South they will need to rethink their tool-kit and learn from other disciplines. We suggest there is a rich tradition to draw upon.




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Advances in Tools to Determine the Glycan-Binding Specificities of Lectins and Antibodies [Reviews]

Proteins that bind carbohydrate structures can serve as tools to quantify or localize specific glycans in biological specimens. Such proteins, including lectins and glycan-binding antibodies, are particularly valuable if accurate information is available about the glycans that a protein binds. Glycan arrays have been transformational for uncovering rich information about the nuances and complexities of glycan-binding specificity. A challenge, however, has been the analysis of the data. Because protein-glycan interactions are so complex, simplistic modes of analyzing the data and describing glycan-binding specificities have proven inadequate in many cases. This review surveys the methods for handling high-content data on protein-glycan interactions. We contrast the approaches that have been demonstrated and provide an overview of the resources that are available. We also give an outlook on the promising experimental technologies for generating new insights into protein-glycan interactions, as well as a perspective on the limitations that currently face the field.




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A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients [Technological Innovation and Resources]

State-of-the-art proteomics-grade mass spectrometers can measure peptide precursors and their fragments with ppm mass accuracy at sequencing speeds of tens of peptides per second with attomolar sensitivity. Here we describe a compact and robust quadrupole-orbitrap mass spectrometer equipped with a front-end High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Interface. The performance of the Orbitrap Exploris 480 mass spectrometer is evaluated in data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes in combination with FAIMS. We demonstrate that different compensation voltages (CVs) for FAIMS are optimal for DDA and DIA, respectively. Combining DIA with FAIMS using single CVs, the instrument surpasses 2500 peptides identified per minute. This enables quantification of >5000 proteins with short online LC gradients delivered by the Evosep One LC system allowing acquisition of 60 samples per day. The raw sensitivity of the instrument is evaluated by analyzing 5 ng of a HeLa digest from which >1000 proteins were reproducibly identified with 5 min LC gradients using DIA-FAIMS. To demonstrate the versatility of the instrument, we recorded an organ-wide map of proteome expression across 12 rat tissues quantified by tandem mass tags and label-free quantification using DIA with FAIMS to a depth of >10,000 proteins.




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StartupWeek Sydney readies for launch

StartupWeek Sydney 2015 starts on Friday, and 5000 people are expected to attend more than 50 events to celebrate and strengthen the city's thriving start-up community.




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Serum non-esterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil and dairy in women

Sandi M. Azab
Mar 31, 2020; 0:jlr.D120000630v1-jlr.D120000630
Methods




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Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease.

Inês Magro dos Reis
Apr 14, 2020; 0:jlr.RA120000632v1-jlr.RA120000632
Research Articles




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WITHDRAWN: Structural and mechanistic studies of hydroperoxide conversions catalyzed by a CYP74 clan epoxy alcohol synthase from amphioxus (Branchiostoma floridae) [Research Articles]

This manuscript has been withdrawn by the Author.




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Serum non-esterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil and dairy in women [Methods]

Nutritional studies rely on various biological specimens for fatty acid (FA) determination, yet it is unclear how levels of serum non-esterified FA (NEFAs) correlate with other circulating lipid pools. Here, we used a high throughput method (< 4 min/sample) based on multisegment injection-non-aqueous-capillary electrophoresis–mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first  identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n=50). Acute changes in serum NEFA trajectories were also studied in non-pregnant women (n=18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum omega-3 (-3) FA correlated with self-reported total -3 daily intake, notably eicosapentaenoic acid (EPA) as its NEFA (r=0.46; p=0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r=0.43; p=0.002), outcomes consistent with results from  total FA serum hydrolysates. In the intervention cohort, serum -3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (p=0.0004). Unlike for docosahexaenoic acid, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r=0.66; p=4.6 x 10-10), and was better suited to detect dietary non-adherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to diet records or food frequency questionnaires.




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Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease. [Research Articles]

Niemann–Pick type C1 (NPC1) disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key-factor in the development of atherosclerosis and non-alcoholic steatohepatitis (NASH). In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring an Npc1 null allele (Npc1nih), creating a dysfunctional NPC1 protein. Npc1nih mice were fed a two or six percent plant stanol esters–enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1nih mice fed the plant stanol–enriched diet exhibited lower hepatic cholesterol accumulation, damage and inflammation than regular chow–fed Npc1nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular towards an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease.




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Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology]

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.




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Erratum: FTY720/fingolimod decreases hepatic steatosis and expression of fatty acid synthase in diet-induced nonalcoholic fatty liver disease in mice [Errata]




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Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice [Research Articles]

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2H/13C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.




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Transketolase Deficiency in Adipose Tissues Protects Mice From Diet-Induced Obesity by Promoting Lipolysis

Obesity has recently become a prevalent health threat worldwide. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and obesity, the role of transketolase (TKT), an enzyme in the non-oxidative branch of the PPP which connects PPP and glycolysis, remains obscure in adipose tissues. In this study, we specifically delete TKT in mouse adipocytes and find no obvious phenotype upon normal diet feeding. However, adipocyte TKT abrogation attenuates high fat diet (HFD)-induced obesity, reduces hepatic steatosis, improves glucose tolerance, alleviates insulin resistance and increases energy expenditure. Mechanistically, TKT deficiency accumulates non-oxidative PPP metabolites, decreases glycolysis and pyruvate input into the mitochondria, leading to increased lipolytic enzyme gene expression and enhanced lipolysis, fatty acid oxidation and mitochondrial respiration. Therefore, our data not only identify a novel role of TKT in regulating lipolysis and obesity, but also suggest limiting glucose-derived carbon into the mitochondria induces lipid catabolism and energy expenditure.




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Maternal Obesity and Western-Style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates

Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a Japanese macaque model to investigate whether maternal obesity combined with a western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed a control or WSD prior to and during pregnancy through lactation, and offspring subsequently weaned to a control or WSD. Muscle glucose uptake and signaling were measured ex vivo in fetal (n=5-8/group) and juvenile offspring (n=8/group). In vivo signaling was evaluated after an insulin bolus just prior to weaning (n=4-5/group). Maternal WSD reduced insulin-stimulated glucose uptake and impaired insulin signaling at the level of Akt phosphorylation in fetal muscle. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and post-weaning WSD and corresponded to modest reductions in insulin-stimulated Akt phosphorylation relative to controls. We conclude that maternal WSD leads to a persistent decrease in offspring muscle insulin-stimulated glucose uptake even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not reverse the effects of maternal WSD on muscle insulin action suggesting earlier interventions may be warranted.




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Genetic lineage tracing with multiple DNA recombinases: A user's guide for conducting more precise cell fate mapping studies [Methods and Resources]

Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, nonspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell-tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage-tracing approach for cell fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell fate mapping. Our review also provides several examples for how to use different types of DNA recombinase–mediated lineage-tracing strategies to improve the resolution of the cell fate mapping in order to probe and explore cell fate–related biological phenomena in the life sciences.




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The High-Fat Diet-Fed Mouse: A Model for Studying Mechanisms and Treatment of Impaired Glucose Tolerance and Type 2 Diabetes

Maria Sörhede Winzell
Dec 1, 2004; 53:S215-S219
Section V: The Incretin Pathway




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Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism




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Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes

Mary C. Gannon
Sep 1, 2004; 53:2375-2382
Pathophysiology




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Autoantibodies in Diabetes

Catherine Pihoker
Dec 1, 2005; 54:S52-S61
Section II: Type 1-Related Forms of Diabetes




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Adapt or Die: The Need for Orders to Evolve

12 June 2019

Adam Ward

Former Deputy Director, Chatham House
Historically, efforts to build rules-based international orders have emerged out of conflict, only for each system to falter when a new crisis emerges. At issue today, with the post-1945 multilateral system under strain, is how to modernize the making and application of rules to break that cycle.

2019-06-07-UN-protest.jpg

School children hold a placard reading "CHANGE" during the Youth Climate Strike May 24, 2019 outside United Nations headquarters in New York City. Photo by Johannes EISELE/AFP/Getty Images.

The most vexing, complicated and elusive question in international relations is how to achieve an order, based on rules, that enjoys legitimacy, rewards investments in cooperation, reconciles clashing interests and deters conflict. It is not a problem over which a magic wand can be waved. But in our own time, immense and patient efforts have been made towards that general goal, however imperfect the result.

The concept of the ‘rules-based international order’ refers today in its most general sense to arrangements put into place to allow for cooperative efforts in addressing geopolitical, economic and other global challenges, and to arbitrate disputes. It is embodied in a variety of multilateral institutions, starting with the United Nations and running through various functional architectures such as the Bretton Woods system, the corpus of international law and other regimes and treaties, down to various regional instances where sovereignty is pooled or where powers have been delegated consensually by states on a particular issue.

Some aspects of the rules-based order are heavily informed by distinct values, such as those contained in the Universal Declaration of Human Rights. But, more often than not, they simply prescribe a set of basic principles for how the business of international political and economic relations is to be transacted. The parameters of legitimate and illegitimate behaviour are specified. Compliance is incentivized, and some scope to sanction transgressors is provided for.

For some, the rules-based international order is a politically highly charged concept. Indeed, the absence of a common standardized definition of it is perhaps a by-product of the controversy which the mere notion of a rules-based order often attracts – among those who had no or little part in its shaping; those who regard multilateralism as an infringement of sovereignty and a straitjacket on national ambitions; and those who sense in it a presumption of universal values and shared interests that jars with their own particular historical experience and political preferences. And in a world in which each country occupies its own place on the spectrum of attraction to, tolerance of and resistance to multilateralism, it is inevitable that the present system should be a patchy and incomplete one.

If that patchiness seems increasingly apparent today, then this reflects the proliferation of problems on a truly global scale that multilateral initiatives have as yet failed to keep up with. This is partly because of the sheer pace of change and the deep complexity of problems, and partly because any significant programme of coordinated action requires a focus and consensus that today is in shrinking supply.

More than that, some of the sharpest challenges – climate change; the lack or weakness of rules in the sea, space and cyber domains; the dilemmas thrown up by technological change – are problematic precisely because they are areas in and through which geopolitical competitions are being contested. The policy challenges may be new, but the pattern of behaviour currently surrounding them presents some dangerous echoes from the past.

Throughout history, most attempts to form international orders have been conceived in a coercive way. From classical antiquity to the 20th century, the dominant form of order has been that imposed or attempted by successive territorial empires, or by predominant powers who made the rules by fiat and were deferred to by their neighbours and satellites.

Significant attempts at more collaborative conceptions of order, aimed at coexistence and minimizing risk through rules and accepted conventions, have been far rarer. And the key point about them is that they have been attempted only after competition has spilled over in an uncontrolled, exhausting and ruinous conflict that has called for mechanisms and understandings to prevent a recurrence of disaster. That, in any case, has been the European experience, and subsequently the result of the engulfing crises that radiated out globally from Europe in the 20th century.

Early efforts at order-building focused on mutual recognition and the management of what were felt to be inevitable rivalries. The Westphalian Peace of 1648 emerged from a 30-year period of religious war in Europe. It emphasized the sanctity of sovereignty and non-interference in the internal affairs of other states as a precondition for order, but relied on a jostling balance-of-power approach to the preservation of a basic stability.

A tolerance of conflicts to correct imbalances was implicit to the scheme. But its acute sensitivity to shifts in alignments of power contributed to the later conflicts – from the wars of the Spanish Succession and Austrian Succession to the Seven Years’ War – that ravaged Europe in the 18th century and occurred in an increasingly global theatre of military operations, tracing the development of European imperial projects.

Despite these shortcomings, the balance-of-power model was produced again as a remedy to uncontrolled conflict, at the Congress of Vienna in 1814–15, following more than 20 years of French Revolutionary and Napoleonic wars. A Concert of Europe, accommodating a rehabilitated France, was instituted to regulate the system and periodically decide major geopolitical issues. But it fell into disuse. And although Europe did not suffer a general war for the rest of the 19th century, the salient geopolitical facts were ones not of power balances but of the sharp relative decline of France and the vertiginous rise of Prussia, which defeated Austria and France on the path to German unification.

These dynamics produced convoluted and ever-widening balancing manoeuvres that by the eve of the First World War in 1914 had congealed and hardened into the opposing Triple Alliance and Triple Entente systems, which trapped their respective members into tangled commitments to fight at the trigger of a crisis.

The peacemaking efforts, in Paris in 1919, that followed the war entailed conscious efforts to overturn the balance-of-power model. The tone was set by US President Woodrow Wilson’s Fourteen Points, with their emphasis on transparency and openness, while the concepts of egalitarianism among states, the drive towards disarmament and the practice of collective security were central to the revolutionary creation of a League of Nations in 1920.

But the peacemaking also included a punitive dimension – the designation of German culpability, the demand of economic reparations and territorial adjustments – imposed by victor on vanquished. To its critics, the international order being evolved, and the rules drafted to underpin it, had the attributes of an involuntary settlement more than those of a construct built by equals.

Lacking a comprehensive membership – crucially, the US had demurred, while other major powers progressively withdrew or were thrown out – and the military means to impose itself, a divided and often circumspect League faltered in meeting a succession of international crises. It then collided fatally with the revanchism of Germany, Italy and Japan that produced the Second World War.

The ambitiousness and eventual institutional intricacy of the UN system founded in 1945 marked a response to the scale of the ordeal through which the world had passed, and sought to correct the deficits of the League. The UN’s membership and the activity of its main organs and specialized agencies all grew prodigiously in succeeding decades, as did its efforts to advance the spirit and culture of multilateralism.

But by giving special privileges to the victors, principally through veto rights held among a small group of permanent Security Council members, the UN reflected and perpetuated a certain historical circumstance: there was no formal institutional adaptation in its highest structures to account for a progressive redistribution of international power, the rehabilitation of defeated countries, the rise of the decolonized world or the desire of emerging powers to assume international responsibilities commensurate with their heft. Rather than a mechanism for international governance, it remained an intergovernmental body through which states pursued their specific or collective priorities.

Indeed, the dominant questions around order in the first five decades of the UN’s existence were those posed by the Cold War conducted by the US and the Soviet Union and their respective allies and satellites, while the UN in effect was a prominent arena in which this global antagonism was carried out.

The world order was bipolar in concentrating power in two camps, with a swath of neutrals, non-aligned and swing players in between; and bi-systemic in the complete contrast in the ideological affinities and economic models that were promoted. Nuclear weapons raised the stakes associated with direct conflict to an existential level, and so pushed armed contests to peripheral theatres or on to skirmishing proxies.

The collapse of communism in the early 1990s ushered in a new dispensation. Those who divined the arrival of a ‘unipolar moment’ for the US were perhaps more accurate in their choice of epithet than they knew. At least on the surface, the US became by far the preponderant power. The decline and 1991 dissolution of the Soviet Union, in consequence of its economic decrepitude and strategic overstretch, not only removed the US’s peer competitor, but also opened up avenues for promoting economic liberalization and democratic government.

This shift was manifest in particular in changing dynamics in Europe. The US had sponsored the reunification of Germany and was a patron of its subsequent embedding in an integrating, democratic and liberal region. Over time, this drew the former Warsaw Pact members into EU and NATO structures (albeit at a pace and with a completeness that Russia’s strategic calculations could not be accommodated to).

And yet, despite these advances, in retrospect the chief development of the 20 years after the Cold War was a different one: globalization had at a gathering pace prompted a redistribution of political power, while its interlocking economic structures created a dense web of interests and dependencies that moved in all directions. It was likely in these circumstances that the appearance of any major emergency would produce insistent voices demanding what they saw as a more inclusive, legitimate and effective form of international order.

Crises duly arrived, first in the shape of the 2003 US-led invasion of Iraq, which strained alliances and stirred controversial debates about the justice and permissibility of military interventions and the need for constraints on US power; and then in the form of the financial meltdown of 2008, seen by many as a principally Western debacle calling for new global economic governance structures as instanced in the improvised G20. Neither set of debates was conclusively resolved, but each persisted against the backdrop of quickening systemic change.

The dilemmas about the shape and maintenance of a rules-based order with multilateralism at its core have since only deepened. The world is pulling in different directions. The ‘America First’ posture of the Trump administration has upturned the central feature of the system. It entails a distaste for multilateral agreements, a disavowal of traditional notions of US leadership, and an insistence on the unimpeded exercise of American power in pursuit of defined national interests.

China asserts the centrality of multilateralism, and practises it selectively, but on the whole favours binary diplomatic transactions where it holds asymmetric advantages; it has used this approach in the construction of its Belt and Road Initiative, as well as on other fronts.

Europe has created in its continent a rules-based order par excellence in the shape of the EU, but its energy has been sapped and its introversion fed by a succession of crises, of which the amputation of the Brexit-bound UK is simply one. The EU has yet to chart its future course or define a global strategy to uphold and advance the multilateralism which has been at its core.

Russia unabashedly is subverting the rules-based order as part of a programme of aggrieved self-aggrandizement. Japan champions the principle of a rules-based system, but the country has been disoriented by its abrupt detachment on this issue from its traditional US partner; while Japan has sought to engage like-minded countries in the West, they have not forged a concerted practical plan of action together.

Among other regional powers, Brazil has a populist government that echoes many of the Trump administration’s instincts, and India, whatever its preferences, has yet to acquire a foreign policy or presence on the global stage equal to its demographic weight and economic potential.

Prominent points of risk in this fragmenting picture are the multilateral trade system, efforts to address climate change, and collective measures to deal with entrenched conflicts.

One obvious consequence of the attrition of the rules-based system through the indifference or ambitions of the great powers is that it will leave smaller states much more exposed and hostage to the vagaries of geopolitical competition. A key question therefore is whether such states will choose and be able to defend a system which gives them a measure of protection.

Over recent decades, a variety of regional groupings – ASEAN, the African Union, the Gulf Cooperation Council, the Organization of American States – have evolved as species of rules-based mechanisms and in order to gather their collective weight. They make a ready constituency for those who would build a coalition for multilateralism. But it is also clear that the support of smaller regional players for such an approach depends on a revision of the rule-making system towards greater inclusivity and a broader say as to the issues it should address.

It is in the context of these trends and structural shifts that Chatham House Expert Perspectives 2019 offers ideas for how to modernize and adapt elements of the rules-based international order. As the title of this opening essay indicates, the imperative to ‘adapt’ reflects the gravity of contemporary challenges, and the inability of many existing structures to underpin ever-more-essential cooperation. Chatham House experts do not offer a master plan, but they attack the problem from a variety of indicative angles.

Suggestions are offered as to where gaps in international rules – regarding economic governance, the global health architecture and in respect of under-regulated domains such as space, for example – need to be filled to address immediate problems and advertise the relevance of multilateralism.

Other ideas demonstrate how logjams affecting some aspects of the system can be worked around; how key powers with scope to shape the system should be engaged; how a broader variety of actors beyond national governments need to be drawn into the effort; how rule-breakers might be tackled; and how imposing order on some chaotic situations requires the fundamental premises of existing policies to be rethought.

Chatham House, which celebrates its centenary in 2020, is a child of efforts after the Great War to reconceive the conduct of international relations and fulfil a mission that is today defined as the creation of a ‘sustainably secure, prosperous and just world’. The historical record shows that international orders not built on these attributes will fail.

This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization.




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Covid-19: Woman with terminal cancer should be released from care home to die with family, says judge




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Fruit Plant Suplemen Diet Herbal Alami - Rahasia Pria

Fruit Plant Original Pelangsing Badan Herbal terbuat dari Sayuran Dan Buah-Buahan Berkualitas Tinggi Mampu Menjadikan Sehat Serta Langsing Secara Cepat



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OBAT PELANGSING BADAN HERBAL FATLOSS DIET ALAMI - Rahasia Pria

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  • Sports and Health

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Pelangsing Badan Herbal Lida Obat Diet Alami - Rahasia Pria

Pelangsing Badan Herbal Lida Daidaihua Adalah Pelangsing Badan Yang Mengandung Bahan Herbal Yang Sangat Cepat Menurunkan Berat Badan, Aman Dan Cepat .



  • Sports and Health

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JDF promises &#039;strong&#039; action against abusive soldiers

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Douglas Orane | Cultural attitudes to enhance productivity - Case Studies numbers five and six

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Frank Robinson, legend and pioneer, dies

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Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice

Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell–specific reduction of HMG-CoA reductase (Hmgcrm–/m–), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcrm–/m– mice than in control Hmgcrfl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcrm–/m– and Hmgcrfl/fl mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell–specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell–specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity.




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Windies players lack commitment – Benjamin

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How scientific are US dietary guidelines?

They have a big impact on the diet of American citizens, and those of most Western nations, so why does the expert advice underpinning US government dietary guidelines not take account of all the relevant scientific evidence asks Nina Teicholz. Read the full investigation: http://www.bmj.com/content/351/bmj.h4962




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How people die remains in the memory of those who live on - supporting the relatives of the dying

All doctors, irrespective of their specialty or the setting in which they work, will care for patients who die. Around half of all deaths occur in hospitals. Evidence suggests that the quality of communication around this process is poorer in hospitals than in other settings, according to responses from relatives who have experienced bereavement....




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How does it feel, to help your patient die?

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Assisted dying: should doctors help patients to die?

The Royal College of Physicians will survey all its members in February on this most controversial question. It says that it will move from opposition to neutrality on assisted dying unless 60% vote otherwise. The BMJ explores several conflicting views. From Canada, palliative care doctor Sandy Buchman explains why he sees medical aid in dying...




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Diet-Induced Type II Diabetes in C57BL/6J Mice

Richard S Surwit
Sep 1, 1988; 37:1163-1167
Original Article




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Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism




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Hickling dies

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Rammya Mathew: Liquid diets offer promise, but we still need upstream solutions