Nanoneedles deliver nucleic acids inside cells

Image from Chiappini et. al.

Gene therapy, the delivery of genetic material to cells in the form of DNA or RNA, has been explored as a means to treat illnesses. These treatments hinge on ourability to getDNA and RNA inside cells, where they can interact with the cell’s machinery. Currently, successful delivery of nucleic acids has been stalled by inefficient insertion of the molecules into cells, safety concerns, limited accessibility of the target cells, and poor scalability.

In order to overcome these limitations, a team of scientists has proposed nanoinjection through a carefully designed array of tiny needles, which they’re calling nanoneedles. Nanoinjection provides a more uniform delivery due to the high density of nanoneedles that can occupy a givensurface area. The researchers fabricated biodegradable, porous nanoneedles from silicon with a geometry that was optimized for intracellular delivery.

The nanoneedles had a 5 m length, 50 m width at the sharp end, and 600 nm base diameter, providing a 300-fold increase in surface area for delivery compared to a non-porous wireof equivalent diameter. The porosity of the needles could also be tailored to modulate things likepayload volume, mechanical strength, and how long the needle persists inside cells.

Characterization of the needles demonstrated they could withstand the force required to penetrate cells and were effective in delivering either DNA or RNA. The nanoneedles progressively dissolved over 36 hours in physiological conditions; after 72 hours only the solid stump remained.

Nanoinjection was tested by either placing nanoneedles beneath or on top of a layer of cells. In both cases, nanoinjection did not induce significant toxicitycells continued tofunction and grow normally over the course of five days. Thenanoneedle constructs were also able to load, retain, and deliver nucleic acids over a 12-18 hour period, achieving uniform RNA spread inside the cellafter 48 hours.

The nanoneedles could deliver two separate types of nucleic acids using a RNA strand and a fluorescently labeled DNA strand. These constructsdemonstrated that the molecules were active once inside the cell; they couldmodulate gene activityby either expressing a gene carried on the DNAor silencing expression of genes via RNA interference.

The efficacy of the device was also tested in rats. The nanoneedles could be used for a localized injection, as shown by their ability to carry fluorescent dyes into the skin and muscle of test rats. Nanoinjection was also assessed on ear and muscle to demonstrate that tissue architecture does not influence the delivery process. Injection of fluorescent dyes did not induce local inflammation withina 24 hour period, and imagingof the skin and muscles revealed that the tissue maintained its normal appearanceafter nanoinjection.

Finally, the researchers compared efficiency of nanoinjection todirect injection of DNA. They tested this usingVEGF165, which is a gene that influences the development of blood vessels. While both injections resulted in expression of human VEGF165 for up to one week, the blood vessels formed were very different.Nano injectionpromoted the formation ofhighly interconnected blood vessels near the surface of the skin and a six-fold increase in overall blood perfusion; direct injection did not.

These nano needles could provide a new route totargeted delivery of RNA and DNA, which could lead to major improvements in efficient gene therapy strategies.

See the article here:

Nanoneedles deliver nucleic acids inside cells

Fluctuation X-ray scattering

IMAGE:In this image, density slices through the center a virus. view more

Credit: Malmerberg et al.

In biology, materials science and the energy sciences, structural information provides important insights into the understanding of matter. The link between a structure and its properties can suggest new avenues for designed improvements of synthetic materials or provide new fundamental insights in biology and medicine at the molecular level.

During standard X-ray solution scattering experiments, molecules tumble around during X-ray exposures, resulting in an angularly isotropic diffraction pattern because of the full orientational averaging of the molecules that scatter X-rays. When X-ray snapshots are collected at timescales shorter than a few nano-seconds, such that molecules are virtually frozen in space and time during the scattering experiment, X-ray diffraction patterns are obtained that are no longer angularly isotropic. These measurements, called fluctuation X-ray scattering, are typically performed on an X-ray free electron laser or on a ultra-bright synchrotron and can provide fundamental insights into the structure of biological molecules, engineered nanoparticles or energy-related mesoscopic materials not attainable via standard scattering methods.

A group of scientists from the Lawrence Berkeley National Laboratory [Malmerberg et al., (2015), IUCrJ, 2, doi:10.1107/S2052252515002535] recently presented an intuitive view of the nature of fluctuation X-ray scattering data and their properties. The scientists have shown that fluctuation scattering is a natural extension of traditional small-angle X-ray scattering and that a number of fundamental operational properties translate from small- and wide-angle X-ray scattering into fluctuation scattering. The authors also show that even with a fairly limited fluctuation scattering dataset, the amount of recoverable structural detail is greatly increased as compared to what can be obtained from standard SAXS/WAXS experiments. Given that the high-quality structural models can be obtained from fluctuation scattering data and the ever-increasing availability of X-ray sources at which these experiments can be performed, the researchers expect that fluctuation scattering experiments will become routine in the future.

“Although fluctuation scattering experiments are not standard or routine at the moment, this work enables us to assess the quality of experimental data and allows us validate our experimental protocols and data reduction routines” Peter Zwart says.

###

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Follow this link:

Fluctuation X-ray scattering

Researchers Testing "Eco-Vapour" Toilet System in India

Washington: A new “eco-vapour” toilet system being tested in India uses a breathable fabric that traps human waste and allows only water vapour molecules to escape, rendering sewage less hospitable to bacteria and other disease-causing organisms.

A team of researchers led by Steven K Dentel, Professor of civil and environmental engineering at the University of Delaware in the US, has been working for several years on a breathable fabric that can be used to line pit toilets and other basic sanitary facilities in developing nations.

The fabric Professor Dentel and his team are developing is similar to that used in sports jackets and raincoats; it only allows tiny water vapour molecules through.

Professor Dentel said this could be a valuable way to filter out liquid water from human waste, letting the pure water escape while retaining everything else.

Funded by the Bill and Melinda Gates Foundation, researchers have been working on the project for some time now.

On December 28, a small group led by doctoral student Shray Saxena headed to India to begin the first field test of the new fabric.

“A lot of people in India right now don’t have improved toilet systems. Even in cities like Kanpur (UP), which are really quite developed, people do not have these facilities available to them,” Shrey said.

Families in two cities, Kanpur and Puri in Odisha, are trying out the new “eco-vapour” toilet system, with sewage collected in 55-gallon drums lined with the breathable fabric, allowing water vapour to evaporate.

The researchers are observing how the fabric performs under varying conditions of heat and humidity, which affect the rate at which water diffuses through the membrane.

If external humidity is high, the lined drums may fill up before enough of the water can evaporate.

See the original post:

Researchers Testing "Eco-Vapour" Toilet System in India

Molecular "Hats" Allow in vivo Activation of Disguised Signaling Peptides

Contact Information

Available for logged-in reporters only

Newswise When someone you know is wearing an unfamiliar hat, you might not recognize them. Georgia Institute of Technology researchers are using just such a disguise to sneak biomaterials containing peptide signaling molecules into living animals.

When the disguised peptides are needed to launch biological processes, the researchers shine ultraviolet light onto the molecules through the skin, causing the hat structures to come off. That allows cells and other molecules to recognize and interact with the peptides on the surface of the material.

This light-activated triggering technique has been demonstrated in animal models, and if it can be made to work in humans, it could help provide more precise timing for processes essential to regenerative medicine, cancer treatment, immunology, stem cell growth, and a range of other areas. The research represents the first time biological signals presented on biomaterials have been activated by light through the skin of a living animal, and could provide a broader platform technology for launching and controlling biological processes in living animals.

Many biological processes involve complex cascades of reactions in which the timing must be very tightly controlled, said Andrs Garca, a Regents Professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech and principal investigator for the project. Until now, we havent had control over the sequence of events in the response to implanted materials. But with this technique, we can deliver a drug or particle with its signal in the off position, then use light to turn the signal on precisely when needed.

Supported by the National Science Foundation and the National Institutes of Health, the research is reported in the December issue of the journal Nature Materials. It resulted from collaboration between scientists from Georgia Tech and the Max-Planck Institute in Germany through the Materials World Network Program.

When biomaterials are introduced into the body, they normally stimulate an immune system response immediately. But the researchers used molecular cages like hats to cover binding sites on the peptides that are normally recognized by cell receptors, preventing recognition by the animals cells. The cages were designed to detach and reveal the peptides when they encounter specific wavelengths of light.

During the five-year project, the research team which included Ted Lee and Jose Garcia from Georgia Tech and Aranzazu del Campo from Max-Planck modified peptides that normally trigger cell adhesion to present the molecular cage in order to disguise them. They showed that disguised peptides introduced into animal models on biomaterials could trigger cell adhesion, inflammation, fibrous encapsulation, and vascularization responses when activated by light. They also showed that the location and timing of activation could be controlled inside the animal by simply shining light through the skin.

The work involved numerous controls to ensure that the triggering observed by the researchers was actually done by exposure of the peptides not the light, or the removal of the protective cage. The researchers also had to demonstrate that the hats were stable enough that they didnt come off spontaneously, but only when the link between the molecular cage and the peptide was severed by the ultraviolet light.

Read this article:

Molecular "Hats" Allow in vivo Activation of Disguised Signaling Peptides

Researchers model how migration of DNA molecules is affected by charge, salt species, and salt concentration

17 hours ago Credit: eugenesergeev / Fotolia.com

Only two mechanisms can move molecules in a fluid. They can follow a temperature gradient or an electrical potential. LMU physicists have modeled how migration of DNA molecules is affected by their charge, the salt species, and salt concentration present in the solution.

Thermophoresis is the migration of molecules in a temperature gradient, migration in an electrical field is termed electrophoresis. Each molecular species reacts to these forces in accordance with its physical characteristics, which determine the velocity and direction of its movement. Some congregate where it is warmer, others prefer the cold; some are drawn to the positive, others move toward the negative pole of a field gradient.

The research group led by Dieter Braun, Professor of Systems Biophysics at LMU and a member of the Nanosystems Initiative Munich (NIM), specializes in the investigation of the thermophoresis of biomolecules. Indeed, their work has given rise to a commercial spin-off, which has developed a rapid and economical analytical method for use in the pharmaceutical industry.

In their latest project, Braun and his colleagues have taken a closer look at how DNA molecules behave in temperature gradients set up within aqueous salt solutions, and constructed a theoretical model that allows them to account for this behavior from first principles. “We have combined several theories that have been proposed to describe why and how molecules move along a temperature gradient,” explains Maren Reichl, who is first author on the new study. “Their electrical charge, the composition and concentrations of the salts in the solution, and the ambient temperature all play a role in how they move. We have measured the effects of these factors experimentally and compared them with our theoretical predictions.”

Interplay of local and global fields

The experiments were carried out in a narrow glass capillary with a diameter of 50 micrometers, filled with a buffered salt solution containing specially designed DNA molecules. A temperature gradient is set up in the solution by heating it locally with a laser. Maren Reichl explains how the behavior of the DNA molecules is detected: “The DNA is labeled with a fluorescent dye, and we use a fluorescence microscope to follow how the DNA migrates away from the heated spot usually toward cooler regions. The level of fluorescence remaining in the heated spot tells us what fraction of the molecules migrates when we raise the temperature of the irradiated volume by 4 degrees, say. And we record the experiment on video, so we can also measure how fast the molecules move out.”

The team found that two factors are primarily responsible for the movement of the molecules. The intrinsic negative charge on each DNA molecule is shielded locally by the positive ions (produced upon dissolution of the added salts) in its immediate vicinity. As a result, an electrical field is generated in the minuscule space between the charged DNA and the counterions surrounding it, which thus acts as a tiny capacitor. The second relevant factor is the global electric field that scales with the temperature gradient. This arises from the so-called Seebeck effect the tendency of ions in the solution to become concentrated in cooler or warmer regions of the liquid, with positive and negative ions moving in opposite directions. This charge separation generates a potential difference, which also influences the movement of the molecules by inducing electrophoresis.

Based on the interplay of local and global electric fields, one can precisely predict their overall effect on a given molecular species. For instance, DNA molecules tend migrate at slower rates in concentrated salt solutions, because the many free ions in the solution more effectively screen the charge on the DNA strands. DNA also moves more slowly in a sodium fluoride solution than in sodium chloride because the electric field associated with the former species more strongly retards the movement of the DNA molecules.

Professor Dieter Braun summarizes the wider significance of the work as follows: “We have, for the first time, convincingly demonstrated that the non-equilibrium phenomenon of thermophoresis can be predicted on the basis of local thermodynamic equilibria. In the next step, we plan to study how molecules compete for the coveted slots in the cold zone. And, of course, we will address the question of why uncharged molecules migrate at all.”

Continue reading here:

Researchers model how migration of DNA molecules is affected by charge, salt species, and salt concentration

Stem Cell Therapy Market in Asia-Pacific to 2018 – Commercialization Supported by Favorable Government Policies …

NEW YORK, April 24, 2013 /PRNewswire/ — Reportlinker.com announces that a new market research report is available in its catalogue:

Stem Cell Therapy Market in Asia-Pacific to 2018 – Commercialization Supported by Favorable Government Policies, Strong Pipeline and Increased Licensing Activity

http://www.reportlinker.com/p01075729/Stem-Cell-Therapy-Market-in-Asia-Pacific-to-2018—Commercialization-Supported-by-Favorable-Government-Policies-Strong-Pipeline-and-Increased-Licensing-Activity.html#utm_source=prnewswire&utm_medium=pr&utm_campaign=Biological_Therapy

Stem Cell Therapy Market in Asia-Pacific to 2018 – Commercialization Supported by Favorable Government Policies, Strong Pipeline and Increased Licensing Activity

Summary

GBI Research, the leading business intelligence provider, has released its latest research “Stem Cell Therapy Market in Asia-Pacific to 2018 – Commercialization Supported by Favorable Government Policies, Strong Pipeline and Increased Licensing Activity”. The report provides an in-depth analysis on stem cell research and development in India, China, Japan, South-Korea and Singapore. The report market analysis and forecasts for CABG, LSCT, Type 1 DM, Type 2 DM, Hearticellgram, Cerecellgram, Cartistem and Cupistem. The report also provides information on trends and pipelines. In addition to this, the report covers market drivers and challenges for stem cell research market.

This report is built using data and information sourced from proprietary databases, primary and secondary research and in-house analysis by GBI Research’s team of industry experts.

GBI Research analysis finds the stem cell therapy market was valued at $545m in 2012, and is projected to grow at a Compound Annual Growth Rate (CAGR) of 10% from 2012 to 2018, to attain a value of $972m in 2018. The market is poised for significant growth in the forecast period due to the anticipated launch of JCR Pharmaceuticals’ JR-031 (2014) in Japan and FCB Pharmicell’s Cerecellgram (CCG) (2015) in South Korea. The research is mainly in early stages, with the majority of the molecules being in early stages of development (Phase I/II and Phase II). Phase I/II and Phase II contribute 67% of the pipeline. Stem cell research is dominated by hospitals/universities/institutions, which contribute 63% of the molecules in the pipeline. The dominance of institutional research is attributable to uncertain therapeutic outcomes in stem cell research.The major companies conducting research in India include Reliance Life Sciences and Stempeutics Research Pvt Ltd, among others. The major institutions include PGIMER and AIIMS.

Scope

– Country analysis of regulatory framework of India, China, South-Korea, Japan and Singapore – In-depth information and analysis on the pipeline products expected to bring a shift to the market positions of the leading manufacturers. – Market characterization data for stem cell research for CABG, LSCT, Type 1 DM, Type 2 DM, Hearticellgram, Cerecellgram, Cartistem and Cupistem. – Key drivers and restraints that have a significant impact on the market. – Competitive landscape of stem cell research in Asia-Pacific. The key companies discussed in this report are Stempeutics, Reliance Lifesciences, International Stem cell services, Shenzhen Beike Biotechnology, JCR Pharmaceuticals, ES Cells International, Stem Cell Technologies i, Pharmicell and Medipost – Key M&A activities, licensing agreements, that have taken place between stem cell companies in 2007 till date.

More here:

Stem Cell Therapy Market in Asia-Pacific to 2018 – Commercialization Supported by Favorable Government Policies …

Stem Cell Therapy Market in Asia-Pacific to 2018 Market Research Report Available at MarketResearchReports.biz

MarketResearchReports.biz Publishes Stem Cell Therapy Market in Asia-Pacific to 2018 Commercialization Supported by Favorable Government Policies, Strong Pipeline and Increased Licensing Activity. Buy the copy of this Report @ http://www.marketresearchreports.biz/analysis-details/stem-cell-therapy-market-in-asia-pacific-to-2018-commercialization-supported-by-favorable-government-policies-strong-pipeline-and-increased-licensing-activity

Albany, NY (PRWEB) March 29, 2013

To Read the Complete Report with TOC Visit: http://www.marketresearchreports.biz/analysis/155690

This report is built using data and information sourced from proprietary databases, primary and secondary research and in-house analysis by GBI Researchs team of industry experts.

GBI Research analysis finds the stem cell therapy market was valued at $545m in 2012, and is projected to grow at a Compound Annual Growth Rate (CAGR) of 10% from 2012 to 2018, to attain a value of $972m in 2018. The market is poised for significant growth in the forecast period due to the anticipated launch of JCR Pharmaceuticals JR-031 (2014) in Japan and FCB Pharmicells Cerecellgram (CCG) (2015) in South Korea.

Related Report: Mobile Health (mHealth) – Enhancing Healthcare and Improving Clinical Outcomes

The research is mainly in early stages, with the majority of the molecules being in early stages of development (Phase I/II and Phase II). Phase I/II and Phase II contribute 67% of the pipeline. Stem cell research is dominated by hospitals/universities/institutions, which contribute 63% of the molecules in the pipeline. The dominance of institutional research is attributable to uncertain therapeutic outcomes in stem cell research.The major companies conducting research in India include Reliance Life Sciences and Stempeutics Research Pvt Ltd, among others. The major institutions include PGIMER and AIIMS.

Latest Report: Global SMB Web Analytics Market 2012-2016

Scope

Country analysis of regulatory framework of India, China, South-Korea, Japan and Singapore

Read the original:

Stem Cell Therapy Market in Asia-Pacific to 2018 Market Research Report Available at MarketResearchReports.biz

Promise seen in deep-learning programs

Using an artificial intelligence technique inspired by theories about how the brain recognizes patterns, technology companies are reporting startling gains in fields as diverse as computer vision, speech recognition and the identification of promising new molecules for designing drugs.

The advances have led to widespread enthusiasm among researchers who design software to perform human activities like seeing, listening and thinking. They offer the promise of machines that converse with humans and perform tasks like driving cars and working in factories, raising the specter of automated robots that could replace human workers.

The technology, called deep learning, has already been put to use in services like Apple’s Siri virtual personal assistant, which is based on Nuance Communications’ speech recognition service, and in Google’s Street View, which uses machine vision to identify specific addresses.

But what is new in recent months is the growing speed and accuracy of deep-learning programs, often called artificial neural networks or just “neural nets” for their resemblance to the neural connections in the brain.

”There has been a number of stunning new results with deep-learning methods,” said Yann LeCun, a computer scientist at New York University who did pioneering research in handwriting recognition at Bell Laboratories. “The kind of jump we are seeing in the accuracy of these systems is very rare indeed.”

Artificial intelligence researchers are acutely aware of the dangers of being overly optimistic. Their field has long been plagued by outbursts of misplaced enthusiasm followed by equally striking declines.

In the 1960s, some computer scientists believed that a workable artificial intelligence system was just 10 years away. In the 1980s, a wave of commercial startups collapsed, leading to what some people called the “AI winter.”

But recent achievements have impressed a wide spectrum of computer experts. In October, for example, a team of graduate students studying with the University of Toronto computer scientist Geoffrey E. Hinton won the top prize, $22,000, in a contest sponsored by Merck to design software to help find molecules that might lead to new drugs.

From a data set describing the chemical structure of 15 different molecules, they used deep-learning software to determine which molecule was most likely to be an effective drug agent.

The achievement was particularly impressive because the team decided to enter the contest at the last minute and designed its software with no specific knowledge about how the molecules bind to their targets. The students were also working with a relatively small set of data; neural nets typically perform well only with very large ones.

Original post:

Promise seen in deep-learning programs

Rising carbon dioxide levels Global warming felt by space junk, satellites around the world – Video



Rising carbon dioxide levels Global warming felt by space junk, satellites around the world
Rising carbon dioxide levels at the edge of space are apparently reducing the pull that Earth's atmosphere has on satellites and space junk, researchers say. The findings suggest that manmade increases in carbon dioxide might be having effects on the Earth that are larger than expected, scientists added. In the layers of atmosphere closest to Earth, carbon dioxide is a greenhouse gas, trapping heat from the sun. Rising levels of carbon dioxide due to human activity are leading to global warming of Earth's surface. However, in the highest reaches of the atmosphere, carbon dioxide can actually have a cooling effect. The main effects of carbon dioxide up there come from its collisions with oxygen atoms. These impacts excite carbon dioxide molecules, making them radiate heat. The density of carbon dioxide is too thin above altitudes of about 30 miles (50 kilometers) for the molecules to recapture this heat, which means it mostly escapes to space, chilling the outermost atmosphere. [ Earth's Atmosphere from Top to Bottom (Infographic) ] Cooling the upper atmosphere causes it to contract, exerting less drag on satellites. Atmospheric drag can have catastrophic effects on items in space mdash; for instance, greater-than-expected solar activity heated the outer atmosphere, increasing drag on Skylab, the first US space station, causing it to crash back to EarthFrom:Johnny DViews:0 0ratingsTime:00:31More inNews Politics

Read the rest here:

Rising carbon dioxide levels Global warming felt by space junk, satellites around the world – Video

Alzheimer's tech spray being developed

A nanotechnology nasal spray is being developed that could transform the early detection and treatment of Alzheimer’s.

The device shoots tiny magnetic particles into the nose which enter the bloodstream and are carried to the brain.

Each particle is fused to an antibody that targets and binds to rogue molecules believed to play an early role in the disease.

Magnetic resonance imaging (MRI) can detect both the particles and the molecules.

To date scientists have only tested the technique in the laboratory on human brain tissue cultures.

But if it can be shown to work in human patients it could lead to a major leap forward in managing Alzheimer’s.

Scientists believe the changes that lead to Alzheimer’s begin decades before the first symptoms appear.

By the time a patient is diagnosed the disease is already far advanced, and experts suspect that is the main reason why a number of promising drugs have failed in patient trials. Identifying the disease much earlier could make it far easier to treat.

Details of the new research were presented at the annual meeting of the Society for Neuroscience in New Orleans, US.

Lead scientist William Klein, from Northwestern University, Chicago, said: “We have created a probe that targets a unique marker of Alzheimer’s disease. This technology is a promising tool for early AD diagnosis and for evaluating the efficacy of investigational new drugs at early stages of the disease.”

Read more from the original source:

Alzheimer's tech spray being developed

Welcome Molecules to Medicine the newest blog at #SciAmBlogs

I am very excited to announce the latest addition to the #SciAmBlogs network Molecules to Medicine, by Dr. Judy Stone.

Judy Stone, MD is an infectious disease specialist, experienced in conducting clinical research. She is the author of Conducting Clinical Research, the essential guide to the topic. As she says, she survived 25 years in solo practice in rural Cumberland, Maryland, and is now broadening her horizons. She particularly loves writing about ethical issues, and tilting at windmills in her advocacy for social justice. As part of her overall desire to save the world when she grows up, she has become especially interested in neglected tropical diseases. When not slaving over hot patients, she can be found playing with photography, friends dogs, or in her garden.

You can check out many years worth of archives on her old blog Politics, Science, and Other Assorted Musings, or follow her on Twitter @drjudystone.

If you are a regular reader of the Scientific American Guest Blog, you have probably read several of Dr.Stones previous posts:

Molecules to Medicine: Clinical Trials for Beginners Molecules to Medicine: From Test-Tube to Medicine Chest Lillys Shocker, or the Post-Marketing Blues Molecules to Medicine: Pharma Trumps HIPAA? Molecules to Medicine: Should pepper spray be put on (clinical) trial? Molecules to Medicine: FDA at a Crossroadsa Tough Place to Be Molecules to Medicine: Plan B: The Tradition of Politics at the FDA Molecules to Medicine: Conscience Clauses versus Refusal: An Historical Perspective Molecules to Medicine: When Religion Collides with Medical Care: Who Decides What Is Right for You? A Taste of #TEDMED 2012: Appetizers A Taste of #TEDMED 2012: Main Course Molecules to Medicine: Have You Thanked a Clinical Researcher Today? Molecules to Medicine: Public Health or Impaired Penises?

Now go and say Hi to Judy in the comments on her first post, then subscribe to or bookmark her blog so you dont miss the future posts.

Continue reading here:

Welcome Molecules to Medicine the newest blog at #SciAmBlogs