SARS-like cluster of circulating bat coronavirus pose threat for human emergence

SARS-like cluster of circulating bat coronavirus pose threat for human emergence
Vineet D. Menachery1, Boyd L. Yount Jr1, Kari Debbink1,2, Sudhakar Agnihothram3, Lisa E. Gralinski1, Jessica A. Plante1, Rachel L. Graham1, Trevor Scobey1, Xing-Yi Ge8, Eric F. Donaldson1, Scott H. Randell4,5, Antonio Lanzavecchia6, Wayne A. Marasco7, Zhengli-Li Shi8, and Ralph S. Baric1,

 

Abstract
The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. In this study, we examine the disease potential for SARSlike CoVs currently circulating in Chinese horseshoe bat populations. Utilizing the SARS-CoV infectious clone, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild type backbone can efficiently utilize multiple ACE2 receptor orthologs, replicate efficiently in primary human airway cells, and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from CoVs utilizing the novel spike protein. Importantly, based on these findings, we synthetically rederived an infectious full length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Together, the work highlights a continued risk of SARS-CoV reemergence from viruses currently circulating in bat populations.

Emerging corona viruses: Genome structure, replication, and pathogenesis

Emerging corona viruses: Genome structure, replication, and pathogenesis
Yu Chen|Qianyun Liu|Deyin Guo
Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China  Center for Infection and Immunity Study, School of Medicine, Sun Yat‐sen University, Guangzhou, China

Abstract

The recent emergence of a novel corona virus (2019‐nCoV), which is causing an out break of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this mini review, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.


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SAC calcium and Virus

SAC calcium and Virus

Viruses originate from RNAs. The sugar in RNA is ribose sugar and is the phosphates based, and they react in the nucleotides to form an ester bond. While not inside a cell or in the process of cell infection, viruses exist as an independent particle known as virions or virus particles. The way the virus replicates dependent on the presence of phosphates in the form of copolymerization with ribose and nucleus. Viruses cannot produce energy for metabolism nor synthesize protein. Hence, to replicate, viruses form the capsid, a protective protein shell, using pre-existing proteins in an infected cell.

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Risk of High Dietary Calcium for Arterial Calcification in Older Adults -Review

Risk of High Dietary Calcium for Arterial Calcification in Older Adults -Review
Nutrients 2013, 5, 3964-3974; doi:10.3390 / nu5103964 / ISSN 2072-6643

Abstract:

 

Concern has recently arisen about the potential adverse effects of excessive calcium intakes, i.e., calcium loading from supplements, on arterial calcification and risks of cardiovascular diseases (CVD) in older adults. Published reports that high calcium intakes in free-living adults have relatively little or no beneficial impact on bone mineral density (BMD) and fracture rates suggest that current recommendations of calcium for adults may be set too high. Because even healthy kidneys have limited capability of eliminating excessive calcium in the diet, the likelihood of soft-tissue calcification may increase in older adults who take calcium supplements, particularly in those with age or disease-related reduction in renal function. The maintenance of BMD and bone health continues to be an important goal of adequate dietary calcium consumption, but eliminating potential risks of CVDs from excessive calcium intakes needs to be factored into policy recommendations for calcium by adults.

Chronic Iron Deficiency as an Emerging Risk Factor for Osteoporosis: A Hypothesis (Review)

Chronic Iron Deficiency as an Emerging Risk Factor for Osteoporosis: A Hypothesis (Review)

Chronic Iron Deficiency as an Emerging Risk Factor for Osteoporosis: A Hypothesis (Review)

Laura Toxqui and M. Pilar Vaquero *

Abstract:

Iron is essential in oxygen transport and participates in many enzymatic systems in the body, with important roles in collagen synthesis and vitamin D metabolism. The relationship between iron and bone health comes from clinical observations in iron overload patients who suffered bone loss. The opposite scenario—whether iron deficiency, with or without anemia, affects bone metabolism—has not been fully addressed. This is of great interest, as this nutrient deficiency is a worldwide public health problem and at the same time osteoporosis and bone alterations are highly prevalent. This review presents current knowledge on nutritional iron deficiency and bone remodeling, the biomarkers to evaluate iron status and bone formation and resorption, and the link between iron and bone metabolism. Finally, it is hypothesized that chronic iron deficiency induces bone resorption and risk of osteoporosis, thus complete recovery from anemia and its prevention should be promoted in order to improve quality of life including bone health. Several mechanisms are suggested; hence, further investigation on the possible impact of chronic iron deficiency on the development of osteoporosis is needed.



 

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

 

 PalmieriV PapaleoV PorcelliP ScarciaL GaitaR SaccoJ HagerF RousseauP CuratoloB ManziR MiliterniC BravaccioS TrilloC SchneiderR MelmedM EliaC LentiM SaccaniT PascucciS Puglisi-AllegraK-L Reichelt & A M Persico

 

Abstract

 

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient–control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca2+). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca2+ chelator ethylene glycol tetraacetic acid; neocortical Ca2+ levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca2+-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca2+ levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca2+ homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.

Intracellular calcium dysregulation in autism spectrum disorder: An analysis of converging organelle signaling pathways

Intracellular calcium dysregulation in autism spectrum disorder: An analysis of converging organelle signaling pathways
ElsevierBiochimica et Biophysica Acta (BBA) – Molecular Cell Research
Volume 1865, Issue 11, Part B, November 2018, Pages 1718-1732

Intracellular calcium dysregulation in autism spectrum disorder: An analysis of converging organelle signaling pathways

Interleukin-1beta Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin*

Interleukin-1beta Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin*

Interleukin-1 Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin*

 

Joseph S. Ainscough‡1, G. Frank Gerberick§, Ian Kimber‡, and Rebecca J. Dearman‡
From the ‡ Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom and the § Procter & Gamble Co. , Cincinnati, Ohio 45253

 

The secretion of IL-1 is a central event in the initiation of inflammation. Unlike most other cytokines, the secretion of IL-1 requires two signals: one signal to induce the intracellular up-regulation of pro-IL-1 and a second signal to drive secretion of the bioactive molecule. The release of pro-IL-1is a complex process involving proteolytic cleavage by caspase-1. However, the exact mechanism of secretion is poorly understood. Here we sought to identify novel proteins involved in IL-1 secretion and intracellular processing to gain further insights into the mechanism of IL-1 release. A human proteome microarray containing 19,951 unique proteins was used to identify proteins that bind human recombinant pro-IL-1. Probes with a signal-to-noise ratio of >3 were defined as biologically relevant. In these analyses, calmodulin was identified as a particularly strong hit, with a signal-to-noise ratio of 11. Using an ELISA-based protein-binding assay, the interaction of recombinant calmodulin with pro-IL-1, but not mature IL-1, was confirmed and shown to be calcium-dependent. Finally, using small molecule inhibitors, it was demonstrated that both calcium and calmodulin were required for nigericin-induced IL-1 secretion in THP-1 cells and primary human monocytes. Together, these data suggest that, following calcium influx into the cell, pro-IL-1 interacts with calmodulin and that this interaction is important for IL-1 processing and release.

Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study

Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study

Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study

Jacquelaine Bartlett, MS,#1 Irene M. Predazzi, PhD,#2 Scott M. Williams, PhD,1 William S. Bush, PhD, MS,3Yeunjung Kim, MD, MPH,4 Stephen Havas, MD, MPH, MS,5 Peter P. Toth, MD, PhD,6 Sergio Fazio, MD, PhD,2 andMichael Miller, MD7

 

 

Abstract

Background—

While the inverse association between high-density lipoprotein cholesterol (HDLC) and risk of (CVD) has been long established, it remains unclear whether low HDL-C remains a CVD risk factor when levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) are not elevated. This is a timely issue because recent studies have questioned whether HDLC is truly an independent predictor of CVD.

Methods and Results—

3590 men and women from the Framingham Heart Study offspring cohort without known CVD were followed between 1987 and 2011. Low HDL-C (<40 mg/dL in men and <50 mg/dL in women) was defined as “isolated” if TG and LDL-C were both low (<100 mg/dL). We also examined higher thresholds for TG (150 mg/dL) and LDL-C (130 mg/dL) and compared low versus high HDL-C phenotypes using logistic regression analysis to assess association with CVD. Compared to isolated low HDL-C, CVD risks were higher when low HDLC was accompanied by LDL-C ≥100 mg/dL and TG <100 mg/dL (OR 1.3 [1.0, 1.6]), TG ≥100mg/dL and LDL-C <100 mg/dL (OR 1.3 [1.1, 1.5]), or TG and LDL-C ≥ 100 mg/dL (OR 1.6, [1.2,2.2]), after adjustment for covariates. When low HDL-C was analyzed with higher thresholds for TG (≥150 mg/dL) and/or LDL-C (≥130 mg/dL) results were essentially the same. In contrast,compared to isolated low HDL-C, high HDL-C was associated with 20-40% lower CVD risk except when TG and LDL-C were elevated.

Conclusions—

CVD risk as a function of HDL-C phenotypes is modulated by other components
of the lipid panel.

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