Tony Pantalleresco Radio Show notes – January 10th 2015

Tony Pantallaresco

Welcom to Tony Pantalleresco Radio Show notes – January 10th 2015

In this show Tony covers the following topics:

Exposure to nanoparticles may threaten heart health

Membrane-Embedded Nanoparticles Induce Lipid Rearrangements Similar to Those Exhibited by Biological Membrane Proteins

Effects of Nanoparticle Charge and Shape Anisotropy on Translocation through Cell Membranes

Could gut microbes help treat brain disorders? Mounting research tightens their connection with the brain

Research linking autism symptoms to gut microbes called ‘groundbreaking’

Bacteria in the gut of autistic children different from non-autistic children

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Exposure to nanoparticles may threaten heart health
Date:

January 8, 2015

Source:

American Technion Society

Nanoparticles, extremely tiny particles measured in billionths of a meter, are increasingly everywhere, and especially in biomedical products. Their toxicity has been researched in general terms, but now a team of Israeli scientists has for the first time found that exposure nanoparticles (NPs) of silicon dioxide (SiO2) can play a major role in the development of cardiovascular diseases when the NP cross tissue and cellular barriers and also find their way into the circulatory system. Their study, published in the December issue of Environmental Toxicology.–The research team was comprised of scientists from the Technion Rappaport Faculty of Medicine, Rambam Medical Center, and the Center of Excellence in Exposure Science and Environmental Health (TCEEH).–“Environmental exposure to nanoparticles is becoming unavoidable due to the rapid expansion of nanotechnology,” says the study’s lead author, Prof. Michael Aviram, of the Technion Faculty of Medicine, “This exposure may be especially chronic for those employed in research laboratories and in high tech industry where workers handle, manufacture, use and dispose of nanoparticles. Products that use silica-based nanoparticles for biomedical uses, such as various chips, drug or gene delivery and tracking, imaging, ultrasound therapy, and diagnostics, may also pose an increased cardiovascular risk for consumers as well.”–In this study, researchers exposed cultured laboratory mouse cells resembling the arterial wall cells to NPs of silicon dioxide and investigated the effects. SiO2 NPs are toxic to and have significant adverse effects on macrophages. a type of white blood cell that take up lipids, leading to atherosclerotic lesion development and its consequent cardiovascular events, such as heart attack or stroke. Macrophages accumulation in the arterial wall under atherogenic conditions such as high cholesterol, triglycerides, oxidative stress — are converted into lipids, or laden “foam cells” which, in turn, accelerate atherosclerosis development.–“Macrophage foam cells accumulation in the arterial wall are a key cell type in the development of atherosclerosis, which is an inflammatory disease” says co-author Dr. Lauren Petrick. “The aims of our study were to gain additional insight into the cardiovascular risk associated with silicon dioxide nanoparticle exposure and discover the mechanisms behind Si02’s induced atherogenic effects on macrophages. We also wanted to use nanoparticles as a model for ultrafine particle (UFP) exposure as cardiovascular disease risk factors.”–Both NPs and UFPs can be inhaled and induce negative biological effects. However, until this study, their effect on the development of atherosclerosis has been largely unknown. Here, researchers have discovered for the first time that the toxicity of silicon dioxide nanoparticles has a “significant and substantial effect on the accumulation of triglycerides in the macrophages,” at all exposure concentrations analyzed, and that they also “increase oxidative stress and toxicity.”–A recent update from the American Heart Association also suggested that “fine particles” in air pollution leads to elevated risk for cardiovascular diseases. However, more research was needed to examine the role of “ultrafine particles” (which are much smaller than “fine particles”) on atherosclerosis development and cardiovascular risk.–“The number of nano-based consumer products has risen a thousand fold in recent years, with an estimated world market of $3 trillion by the year 2020,” conclude the researchers. “This reality leads to increased human exposure and interaction of silica-based nanoparticles with biological systems. Because our research demonstrates a clear cardiovascular health risk associated with this trend, steps need to be taken to help ensure that potential health and environmental hazards are being addressed at the same time as the nanotechnology is being developed.Story Source-The above story is based on materials provided by American Technion Society. The original article was written by Kevin Hattori. Note: Materials may be edited for content and length.Journal Reference-Lauren Petrick, Mira Rosenblat, Nicole Paland, Michael Aviram. Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation. Environmental Toxicology, 2014; DOI: 10.1002/tox.22084

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Membrane-Embedded Nanoparticles Induce Lipid Rearrangements Similar to Those Exhibited by Biological Membrane Proteins

Abstract

Amphiphilic monolayer-protected gold nanoparticles (NPs) have recently been shown to spontaneously fuse with lipid bilayers under typical physiological conditions. The final configuration of these NPs after fusion is proposed to be a bilayer-spanning configuration resembling transmembrane proteins. In this work, we use atomistic molecular dynamics simulations to explore the rearrangement of the surrounding lipid bilayer after NP insertion as a function of particle size and monolayer composition. All NPs studied induce local bilayer thinning and a commensurate decrease in local lipid tail order. Bilayer thickness changes of similar magnitude have been shown to drive protein aggregation, implying that NPs may also experience a membrane-mediated attraction. Unlike most membrane proteins, the exposed surface of the NP has a high charge density that causes electrostatic interactions to condense and reorient nearby lipid head groups. The decrease in tail order also leads to an increased likelihood of lipid tails spontaneously protruding toward solvent, a behavior related to the kinetic pathway for both NP insertion and vesicle–vesicle fusion. Finally, our results show that NPs can even extract lipids from the surrounding bilayer to preferentially intercalate within the exposed monolayer.[F1] These drastic lipid rearrangements are similar to the lipid mixing encouraged by fusion peptides, potentially allowing these NPs to be tuned to perform a similar biological function. This work complements previous studies on the NP–bilayer fusion mechanism by detailing the response of the bilayer to an embedded NP and suggests guidelines for the design of nanoparticles that induce controllable lipid rearrangements.

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Effects of Nanoparticle Charge and Shape Anisotropy on Translocation through Cell Membranes

Nanotoxicity is becoming a major concern as the use of nanoparticles in imaging, therapeutics, diagnostics, catalysis, sensing, and energy harvesting continues to grow dramatically. The tunable functionalities of the nanoparticles offer unique chemical interactions in the translocation process through cell membranes. The overall translocation rate of the nanoparticle can vary immensely on the basis of the charge of the surface functionalization along with shape and size. Using advanced molecular dynamics simulation techniques, we compute translocation rate constants of functionalized cone-, cube-, rod-, rice-, pyramid-, and sphere-shaped nanoparticles through lipid membranes. The computed results indicate that depending on the nanoparticle shape and surface functionalization charge, the translocation rates can span 60 orders of magnitude. Unlike isotropic nanoparticles, positively charged, faceted, rice-shaped nanoparticles undergo electrostatics-driven reorientation in the vicinity of the membrane to maximize their contact area and translocate instantaneously, disrupting lipid self-assembly and thereby causing significant membrane damage. In contrast, negatively charged nanoparticles are electrostatically repelled from the cell membrane and are less likely to translocate.[F2] Differences in translocation rates among various shapes may have implications on the structural evolution of pathogens from spherical to rodlike morphologies for enhanced efficacy.

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Could gut microbes help treat brain disorders? Mounting research tightens their connection with the brain
Date:

January 8, 2015

Source:

Kavli Foundation

The trillions of microbes that inhabit the human body, collectively called the microbiome, are estimated to weigh two to six pounds — up to twice the weight of the average human brain. Most of them live in the gut and intestines, where they help us to digest food, synthesize vitamins and ward off infection. But recent research on the microbiome has shown that its influence extends far beyond the gut, all the way to the brain.–Over the past 10 years, studies have linked the gut microbiome to a range of complex behaviors, such as mood and emotion, and appetite and satiety. Not only does the gut microbiome appear to help maintain brain function but it may also influence the risk of psychiatric and neurological disorders, including anxiety, depression and autism[F3] .—Three researchers at the forefront of this emerging field recently discussed the microbiome-brain connection with The Kavli Foundation.–“The big question right now is how the microbiome exerts its effects on the brain,” said Christopher Lowry, Associate Professor of Integrative Physiology at the University of Colorado, Boulder. Lowry is studying whether beneficial microbes can be used to treat or prevent stress-related psychiatric conditions, including anxiety and depression.–One surprising way in which the microbiome influences the brain is during development. Tracy Bale, Professor of Neuroscience at the School of Veterinary Medicine at the University of Pennsylvania, and her team have found that the microbiome in mice is sensitive to stress and that stress-induced changes to a mother’s microbiome are passed on to her baby and alter the way her baby’s brain develops.–“There are key developmental windows when the brain is more vulnerable because it’s setting itself up to respond to the world around it,” said Bale, who has done pioneering research into the effects of maternal stress on the brain. “So, if mom’s microbial ecosystem changes — due to infection, stress or diet, for example — her newborn’s gut microbiome will change too, and that can have a lifetime effect.”—Sarkis Mazmanian, Louis & Nelly Soux Professor of Microbiology at the California Institute of Technology, is exploring the link between gut bacteria, gastrointestinal disease and autism, a neurodevelopmental disorder. He has discovered that the gut microbiome communicates with the brain via molecules that are produced by gut bacteria and then enter the bloodstream. These metabolites are powerful enough to change the behavior of mice.

“We’ve shown, for example, that a metabolite produced by gut bacteria is sufficient to cause behavioral abnormalities associated with autism and with anxiety when it is injected into otherwise healthy mice,” said Mazmanian.—The work of these three researchers raises the possibility that brain disorders, including anxiety, depression and autism, may be treated through the gut, which is a much easier target for drug delivery than the brain. But there is still much more research to be done to understand the gut-microbiome-brain connection, they said.—Mazmanian’s lab is also exploring whether the microbiome plays a role in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.”There are flash bulbs going off in the dark, suggesting that very complex neurodegenerative disorders may be linked to the microbiome. But once again this is very speculative. These seminal findings, the flash bulbs, are only just beginning to illuminate our vision of the gut-microbiome-brain connection,” said Mazmanian.–Story Source-The above story is based on materials provided by Kavli Foundation. Note: Materials may be edited for content and length.

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Research linking autism symptoms to gut microbes called ‘groundbreaking’
Date:

December 19, 2013

Source:

University of Colorado at Boulder

A new study showing that feeding mice a beneficial type of bacteria can ameliorate autism-like symptoms is “groundbreaking,” according to University of Colorado Boulder Professor Rob Knight, who co-authored a commentary piece about the research appearing in the current issue of the journal Cell.-The autism study, published today in the same issue of Cell, strengthens the recent scientific understanding that the microbes that live in your gut may affect what goes on in your brain. It is also the first to show that a specific probiotic may be capable of reversing autism-like behaviors in mice.–“The broader potential of this research is obviously an analogous probiotic that could treat subsets of individuals with autism spectrum disorder,” wrote the commentary authors, who also included CU-Boulder Research Associate Dorota Porazinska and doctoral student Sophie Weiss.–The study underscores the importance of the work being undertaken by the newly formed Autism Microbiome Consortium, which includes Knight as well as commentary co-authors Jack Gilbert of the University of Chicago and Rosa Krajmalnik-Brown of Arizona State University. The interdisciplinary consortium — which taps experts in a range of disciplines from psychology to epidemiology — is investigating the autism-gut microbiome link.

For the new Cell study, led by Elaine Hsiao of the California Institute of Technology, the researchers used a technique called maternal immune activation in pregnant mice to induce autism-like behavior and neurology in their offspring. The researchers found that the gut microbial community of the offspring differed markedly compared with a control group of mice. When the mice with autism-like symptoms were fed Bacteriodes fragilis,[F4] a microbe known to bolster the immune system, the aberrant behaviors were reduced.–Scientific evidence is mounting that the trillions of microbes that call the human body home can influence our gut-linked health, affecting our risk of obesity, diabetes and colon cancer, for example. But more recently, researchers are discovering that gut microbes also may affect neurology — possibly impacting a person’s cognition, emotions and mental health, said Knight, also a Howard Hughes Medical Institute Early Career Scientist and an investigator at CU-Boulder’s BioFrontiers Institute.–The Autism Microbiome Consortium hopes to broaden this understanding by further studying the microbial community of autistic people, who tend to suffer from more gastrointestinal problems than the general public.-People with autism spectrum disorder who would like to have their gut microbes sequenced can do so now through the American Gut Project, a crowdfunded research effort led by Knight.-The consortium also includes Catherine Lozupone and Kimberly Johnson of CU-Boulder, James Adams of Arizona State University, Mady Hornig of Columbia University, Sarkis Mazmanian of the California Institute of Technology, John Alverdy of the University of Chicago and Janet Jansson of Lawrence Berkeley Lab.-Story Source-The above story is based on materials provided by University of Colorado at Boulder. Note: Materials may be edited for content and length.-Journal Reference-Jack A. Gilbert, Rosa Krajmalnik-Brown, Dorota L. Porazinska, Sophie J. Weiss, Rob Knight. Toward Effective Probiotics for Autism and Other Neurodevelopmental Disorders. Cell, 2013; 155 (7): 1446 DOI: 10.1016/j.cell.2013.11.035

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Bacteria in the gut of autistic children different from non-autistic children
Date:

January 11, 2012

Source:

American Society for Microbiology

The underlying reason autism is often associated with gastrointestinal problems is an unknown, but new results to be published in the online journal mBio® on January 10 reveal that the guts of autistic children differ from other children in at least one important way: many children with autism harbor a type of bacteria in their guts that non-autistic children do not. -The study was conducted by Brent Williams and colleagues at the Mailman School of Public Health at Columbia University.–Earlier work has revealed that autistic individuals with gastrointestinal symptoms often exhibit inflammation and other abnormalities in their upper and lower intestinal tracts. However, scientists do not know what causes the inflammation or how the condition relates to the developmental disorders that characterize autism. The research results appearing in mBio® indicate the communities of microorganisms that reside in the gut of autistic children with gastrointestinal problems are different than the communities of non-autistic children. Whether or not these differences are a cause or effect of autism remains to be seen.–“The relationship between different microorganisms and the host and the outcomes for disease and development is an exciting issue,” says Christine A. Biron, the Brintzenhoff Professor of Medical Science at Brown University and editor of the study. “This paper is important because it starts to advance the question of how the resident microbes interact with a disorder that is poorly understood.”–Bacteria belonging to the group Sutterella represented a relatively large proportion of the microorganisms found in 12 of 23 tissue samples from the guts of autistic children, but these organisms were not detected in any samples from non-autistic children. Why this organism is present only in autistic kids with gastrointestinal problems and not in unaffected kids is unclear.-“Sutterella has been associated with gastrointestinal diseases below the diaphragm, and whether it’s a pathogen or not is still not clear,” explains Jorge Benach, Chairman of the Department of Microbiology at Stony Brook University and a reviewer of the report. “It is not a very well-known bacterium.”–In children with autism, digestive problems can be quite serious and can contribute to behavioral problems, making it difficult for doctors and therapists to help their patients. Autism, itself, is poorly understood, but the frequent linkage between this set of developmental disorders and problems in the gut is even less so.–Benach says the study was uniquely powerful because they used tissue samples from the guts of patients. “Most work that has been done linking the gut microbiome with autism has been done with stool samples,” says Benach, but the microorganisms shed in stool don’t necessarily represent the microbes that line the intestinal wall.[F5] “What may show up in a stool sample may be different from what is directly attached to the tissue,” he says.–Tissue biopsy samples require surgery to acquire and represent a difficult process for the patient[F6] , facts that underscore the seriousness of the gastrointestinal problems many autistic children and their families must cope with.–Benach emphasizes that the study is statistically powerful, but future work is needed to determine what role Sutterella plays, if any, in the problems in the gut. “It is an observation that needs to be followed through,” says Benach.—Story Source-The above story is based on materials provided by American Society for Microbiology. Note: Materials may be edited for content and length.

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TOP B

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[F1]This is how the nanoparticles can accumalte by integrating with cells fats 000using proteins or sugars in the body to align and replicate in the system

[F2]Interesting —negative charge would repel NP from fats

[F3]Would come from glyphosate poisoning due to the way it removes all healthy bacteria from the colon and protects all the negative—without the health bacteria in place any foreign metal—biofilm could then by pass the blood brain barrier and cause imbalances not to mention digestive disorders as well

[F4]Anaerobic bacteria remain an important cause of bloodstream infections and account for 1–17% of positive blood cultures. This review summarizes the epidemiology, microbiology, predisposing conditions, and treatment of anaerobic bacteremia (AB) in newborns, children, adults and in patients undergoing dental procedures. The majority of AB are due to Gram-negative bacilli, mostly Bacteroides fragilis group. The other species causing AB include Peptostreptococcus, Clostridium spp., and Fusobacterium spp. Many of these infections are polymicrobial. AB in newborns is associated with prolonged labor, premature rupture of membranes, maternal amnionitis, prematurity, fetal distress, and respiratory difficulty. The predisposing conditions in children include: chronic debilitating disorders such as malignant neoplasm, hematologic abnormalities, immunodeficiencies, chronic renal insufficiency, or decubitus ulcers and carried a poor prognosis. Predisposing factors to AB in adults include malignant neoplasms, hematologic disorders, transplantation of organs, recent gastrointestinal or obstetric gynecologic surgery, intestinal obstruction, diabetes mellitus, post-splenectomy, use of cytotoxic agents or corticosteroids, and an undrained abscess. Early recognition and appropriate treatment of these infections are of great clinical importance.

[F5]And when you consider nanoparticles and there disruptive role on cellular functions and genetics with the disrupting of gene programming and glyphosates which flush out healthy bacteria and protect the negative —these are factors that will not show up with conventional testing—we are dealing with this on a nanoscale —

[F6]The tissue samples would be required in order to see what is actually in the lining of the intestines—with the current scopes today they cannot access the information