A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

A chronology of key events

Key facts, figures and dates

A chronology of key events

Key facts, figures and dates

A chronology of key events

A chronology of key events

A chrtonology of key events

A chronology of key events from 1916 to 2007.

A chronology of key events

A chronology of key events

(University of British Columbia) Mars had a global magnetic field much earlier -- and much later -- than previously known. Analysis of new satellite data found clear evidence of a magnetic field coming from a lava flow that formed less than 3.7 billion years ago, half a billion years after many people thought the Martian dynamo had ceased. The researchers also detected low-intensity magnetic fields over the Borealis Basin, believed to be one of the oldest features on Mars.

(American Geriatrics Society) The American Geriatrics Society (AGS) and the AGS Health in Aging Foundation today conferred one of their newest honors, the Arti Hurria Memorial Award for Emerging Investigators in Internal Medicine Focused on the Care of Older Adults, on two experts: Rasheeda Hall, MD, a board-certified nephrologist and assistant professor of medicine at Duke University; and Kah Poh (Melissa) Loh, MBBCh, BAO, a board-certified internist, hematologist, and oncologist at the University of Rochester Medical Center.

Sodium glucose co-transporter-2 inhibitors (SGLT2i) have favorable cardiovascular outcomes in diabetic patients. However, whether SGLT2i can improve obesity-related cardiac dysfunction is unknown. Sestrin2 is a novel stress-inducible protein that regulates AMPK-mTOR and suppresses oxidative damage. The aim of this study was to determine whether empagliflozin (EMPA) improves obesity-related cardiac dysfunction via regulating Sestrin2-mediated pathways in diet-induced obesity. C57BL/6J mice and Sestrin2 knockout mice were fed a high-fat diet (HFD) for 12 weeks and then treated with or without EMPA (10 mg/kg) for 8 weeks. Treating HFD-fed C57BL/6J mice with EMPA reduced body weight, whole-body fat, and improved metabolic disorders. Furthermore, EMPA improved myocardial hypertrophy/fibrosis and cardiac function, and reduced cardiac fat accumulation and mitochondria injury. Additionally, EMPA significantly augmented Sestrin2 levels, increased AMPK and eNOS phosphorylation, but inhibited Akt and mTOR phosphorylation. These beneficial effects were partially attenuated in HFD-fed Sestrin2 knockout mice. Intriguingly, EMPA treatment enhanced the Nrf2/HO-1-mediated oxidative stress response, suggesting antioxidant and anti-inflammatory activity. Thus, EMPA improved obesity-related cardiac dysfunction via regulating Sestrin2-mediated AMPK-mTOR signaling and maintaining redox homeostasis. These findings provide a novel mechanism for the cardiovascular protection of SGLT2i in obesity.

A failure in self-tolerance leads to autoimmune destruction of pancreatic β-cells and type 1 diabetes (T1D). Low molecular weight dextran sulfate (DS) is a sulfated semi-synthetic polysaccharide with demonstrated cytoprotective and immunomodulatory properties in vitro. However, whether DS can protect pancreatic β-cells, reduce autoimmunity and ameliorate T1D is unknown. Here we report that DS, but not dextran, protects human β-cells against cytokine-mediated cytotoxicity in vitro. DS also protects mitochondrial function and glucose-stimulated insulin secretion and reduces chemokine expression in human islets in a pro-inflammatory environment. Interestingly, daily treatment with DS significantly reduces diabetes incidence in pre-diabetic non-obese diabetic (NOD) mice, and most importantly, reverses diabetes in early-onset diabetic NOD mice. DS decreases β-cell death, enhances islet heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG) expression and preserves β-cell mass and plasma insulin in these mice. DS administration also increases the expression of the inhibitory co-stimulatory molecule programmed death-1 (PD-1) in T-cells, reduces interferon-+ CD4+ and CD8+ T-cells and enhances the number of FoxP3+ cells. Collectively, these studies demonstrate that the action of one single molecule, DS, on β-cell protection, extracellular matrix preservation and immunomodulation can reverse diabetes in NOD mice highlighting its therapeutic potential for the treatment of T1D.

Mitochondrial protein FAM3A suppresses hepatic gluconeogenesis and lipogenesis. This study aimed to screen drug(s) that activates FAM3A expression and evaluate its effect(s) on hyperglycemia and steatosis. Drug-repurposing methodology predicted that antidepressive drug doxepin was among the drugs that potentially activated FAM3A expression. Doxepin was further validated to stimulate the translocation of transcription factor HNF4α from the cytoplasm into the nucleus, where it promoted FAM3A transcription to enhance ATP synthesis, suppress gluconeogenesis, and reduce lipid deposition in hepatocytes. HNF4α antagonism or FAM3A deficiency blunted doxepin-induced suppression on gluconeogenesis and lipid deposition in hepatocytes. Doxepin administration attenuated hyperglycemia, steatosis, and obesity in obese diabetic mice with upregulated FAM3A expression in liver and brown adipose tissues (BAT). Notably, doxepin failed to correct dysregulated glucose and lipid metabolism in FAM3A-deficient mice fed on high-fat diet. Doxepin’s effects on ATP production, Akt activation, gluconeogenesis, and lipogenesis repression were also blunted in FAM3A-deficient mouse livers. In conclusion, FAM3A is a therapeutic target for diabetes and steatosis. Antidepressive drug doxepin activates FAM3A signaling pathways in liver and BAT to improve hyperglycemia and steatosis of obese diabetic mice. Doxepin might be preferentially recommended as an antidepressive drug in potential treatment of patients with diabetes complicated with depression.

Meritxell Morró
May 1, 2020; 69:927-939
Islet Studies

The number of people estimated to be latently infected with TB - that is infected with TB, which has not yet manifested symptoms - is around 2 billion. That is 1 in 3 people on the planet are infected by the bacteria. The World Health Organization’s website notes that on average 5-10% of those infected with TB will develop active TB. That number...

Schwann cell–derived exosomes communicate with dorsal root ganglia (DRG) neurons. The current study investigated the therapeutic effect of exosomes derived from healthy Schwann cells (SC-Exos) on diabetic peripheral neuropathy (DPN). We found that intravenous administration of SC-Exos to type 2 diabetic db/db mice with peripheral neuropathy remarkably ameliorated DPN by improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity. These functional improvements were associated with the augmentation of epidermal nerve fibers and remyelination of sciatic nerves. Quantitative RT-PCR and Western blot analysis of sciatic nerve tissues showed that SC-Exo treatment reversed diabetes-reduced mature form of miRNA (miR)-21, -27a, and -146a and diabetes-increased semaphorin 6A (SEMA6A); Ras homolog gene family, member A (RhoA); phosphatase and tensin homolog (PTEN); and nuclear factor-B (NF-B). In vitro data showed that SC-Exos promoted neurite outgrowth of diabetic DRG neurons and migration of Schwann cells challenged by high glucose. Collectively, these novel data provide evidence that SC-Exos have a therapeutic effect on DPN in mice and suggest that SC-Exo modulation of miRs contributes to this therapy.

Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H₂O₂) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H₂O₂ by high glucose, and H₂O₂ reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.

The U.S. Coast Guard named Rear Adm. Melissa Bert as its first female judge advocate and chief counsel, its top legal position.

I love a carrot cake . Usually walnuts are used however who doesn't want to take advantage of the local new season pecans at our local markets . Happy baking!

Plenty of pears around at the moment. This sauce is a nice alternative to the traditional apple sauce with pork.

Gould, Elizabeth, 1804-1841 -- Fiction.

Aboriginal Australians -- Fiction.

Secrecy -- Juvenile fiction.

A macro depiction of a beetle called Epilachna chrysomelina

A look at the two major political parties' platforms since the first charter school law was passed shows how Democrats' positions on school choice have evolved, including increased calls for accountability.

After two prosecutors recused themselves from investigating Ahmaud Arbery's death, Gregory and Travis McMichael were arrested.

Some of the most important pre-literacy skills begin in infancy. This timeline shows examples of the milestones children meet on their path to fluent reading.

Relaxation in adherence to prescribed timelines issued by SEBI due to COVID 19

he Division of Public Health (DPH) is providing updated information regarding a potential Hepatitis A exposure at a Buffalo Wild Wings food establishment in Middletown, which was announced on Thursday, April 11, 2019.

The Association of Power Producers (APP) had requested Coal India Ltd (CIL) to extend the timelines for the auction as well as reassess the eligibility for participation in the third round of auction under the SHAKTI B (ii) scheme.

Trade unions are of the view that the retirement fund body should set a definite timeline for employers to deposit the money already deducted from employee’s monthly salary.

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The move comes after renewable companies made representations to the government to allow a blanket extension for six months to overcome supply-side disruptions in completing the projects.

At Sake Lovers Inc., founder Yuki Imanishi works with 100 small breweries across Japan to promote their products and connect them directly with consumers.