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A massive boom heard Wednesday night over Puget Sound on the northwestern coast of Washington was most likely an exploding meteor. Or that's what They want us to believe anyway. The American Meteor Society registered a dozen reports. Video above. Keep your eyes on the upper left of the frame.

"The more I read the more inclined I am to believe this was a fireball (which is a meteor that is larger and brighter than normal)," the American Meteor Society's Bob Lunsford said. "I'm certain now that this was a meteoric event."

From KOMONews:

Most meteors' explosions are heard about a minute or two after they explode due to the time it takes the sound to reach the Earth's surface, Lunsford said. Sound travels at 767 mph in standard atmosphere conditions, indicating this fireball exploded some 35 miles away.

"If this was larger than normal then the sound could have originated from a higher altitude. So a delay of 3 minutes is entirely possible," Lunsford said. "Meteors become visible at a height of around 50 miles so your estimate is well within that range."

Lunsford said because there was a boom, it’s very likely there are small, rock-sized pieces of the meteor somewhere on the ground. When a meteor causes a boom, it’s “pretty far down” in the atmosphere.

Read the rest

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The following article, Rush Limbaugh Predicts Joe Biden Won’t Be The Dem Nominee: “Something’s Gonna Happen”, was first published on 100PercentFedUp.com.

Is Joe Biden going to become the Democrat nominee and run against Trump in the fall?

Continue reading: Rush Limbaugh Predicts Joe Biden Won’t Be The Dem Nominee: “Something’s Gonna Happen” ...

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function.

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research

Ivan Matic
Jan 1, 2008; 7:132-144
Research

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research

William M. Old
Oct 1, 2005; 4:1487-1502
Research

Leigh Anderson
Apr 1, 2006; 5:573-588
Research

Jesper V. Olsen
Dec 1, 2005; 4:2010-2021
Technology

Invitation Only Research Event

Event participants

Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of Chicago
Tom Gillhespy, Principal Consultant, Itad
Shodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)
Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House

Jennifer L. Macdonald
May 1, 2005; 46:1061-1067
Methods

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

M el-Saadani
Apr 1, 1989; 30:627-630
Articles

WS Harris
Jun 1, 1989; 30:785-807
Reviews

M. Burstein
Nov 1, 1970; 11:583-595
Articles

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

Vitali Matyash
May 1, 2008; 49:1137-1146
Methods

S Eisenberg
Oct 1, 1984; 25:1017-1058
Reviews

Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews

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

William R. Morrison
Oct 1, 1964; 5:600-608
Articles

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

Invitation Only Research Event

Event participants

Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of Chicago
Tom Gillhespy, Principal Consultant, Itad
Shodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)
Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House