Saturday, 27 January 2018

EBOLA: PAPER TEST DIAGNOSIS UNVEILED

To combat deadly outbreaks of Ebola, researchers need a variety of simple, portable tests that help them control and treat infections. Now researchers have developed a paper-based strip that detects immunity against this viral infection. The new test uses a color-changing paper strip similar to store-bought pregnancy kits and is read using a smartphone.
Traditional lab tests for detecting the Ebola virus require advanced facilities and take days to give results. Scientists have recently developed strip-based tests that directly detect the Ebola virus by spotting the antigens it produces. But right now, doctors don’t have access to a fast, field-based test for detecting the antibodies that humans produce to fight those antigens. “Understanding a survivor’s immune response to the disease could be really useful in understanding the spread of the disease and in helping with future management,” says Molly M. Stevens, a professor of biomedical materials & regenerative medicine at Imperial College London.
Stevens and her colleagues made their new test using commercially available paper test strips. They engineered three antigens produced by different subtypes of the Ebola virus and printed lines of the protein solutions on one end of the strips. To perform the test, a few microliters of blood serum are loaded on the other end of the strip, followed by a solution of selective antibodies that will bind to the target Ebola antibodies and label them with 40-nm-wide gold nanoparticles.
The serum and the antibody solution wick along a thin channel towards the protein test lines. Ebola antibodies in the serum sample bind to the gold nanoparticles and then to the lines of proteins. The nanoparticles aggregate and reflect light, turning the test lines reddish-purple within 15 minutes.
A smartphone app developed by the team measures the intensity of the line colors from a photograph of the test strip. An intensity above a preset threshold—determined using serum from non-infected volunteers—indicates positive for Ebola antibodies. The app also allows clinicians to add patient details and geographical location to help create a map to observe disease location and spread.
The team validated the method using serum samples from 121 people in Uganda: 90 Ebola survivors and 31 non-infected local residents. Compared with results from standard lab-based enzyme-linked immunosorbent assay (ELISA), the test was 100% accurate at detecting individuals who had survived Ebola, and gave one false positive with an uninfected sample. The test strips worked with both fresh and thawed serum samples and after being stored for 16 weeks in low humidity at room temperature. The team is now working on a whole-blood test that wouldn’t require isolating the serum to make it even easier to use in remote areas.
Medical workers in rural clinics could use the new test to identify an Ebola patient’s immune response to the disease. “Understanding who is more likely and less likely to survive could help to decide on the best treatment and care,” Stevens says. It could, for instance, help determine how best to allocate limited resources.
What’s more, the system offers a way for researchers to help control the spread of the disease by monitoring and mapping it, and even prevent future outbreaks by developing vaccines. “If an Ebola vaccine were developed, the test would also be useful for identifying individuals who would not need immunization,” says Lee Gehrke, a professor of microbiology & immunology at Massachusetts Institute of Technology, who was not involved in the work.
The researchers still need to validate the test with a larger population of survivors located across a broader area, says Kimberly Hamad-Schifferli, professor of mechanical & biological engineering at MIT, who also was not involved in the study. “Other regions may have new forms of the virus that are slightly different.”

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Thursday, 25 January 2018

FERTILIZER SUBSIDY: LOW PRESSURE AMMONIA PRODUCTION

Lanthanum–cobalt catalyst that breaks nitrogen triple bond under mild conditions could revolutionise small-scale ammonia synthesis
Structural properties of LaCoSi. a Lattice structure of LaCoSi
Structure of the lanthanum–cobalt–silicon catalyst

Rather than relying on ammonia made by the energy-hungry Haber–Bosch process, local fertiliser synthesis could soon be possible with a catalyst that can break the nitrogen–nitrogen triple bond at ambient pressure.
Ammonia, one of the key ingredients in fertilisers, is made on a huge scale by the only reaction that can reliably break the strong dinitrogen bond: the Haber–Bosch process. However, the reaction needs extreme conditions – pressures of around 20MPa and temperatures of at least 400°C – which requires specialised equipment and a lot of energy. Currently, the Haber–Bosch process makes around 140 million tonnes of ammonia per year, consuming around 2% of the world’s energy output in the process.
However, a discovery made by a team led by Hideo Hosono and Junjie Wang from the Tokyo Institute of Technology, Japan, could one day cut down on those sizeable energy requirements: a lanthanum–cobalt–silicon (LaCoSi) catalyst that can break the nitrogen–nitrogen bond at ambient pressure. At 400°C, the catalyst is 10 times more efficient at making ammonia under the same conditions as its closest competitor, a cobalt–molybdenum nitride. The only other catalyst that comes close to LaCoSi’s performance contains the rare and expensive metal ruthenium.
LaCoSi is one of a family of intermetallic compounds that contains a rare earth, a transition metal and a p-block element. In this setup, cobalt is very electron-rich, which allows it to break stable bonds such as the H2 or the N2 bond. This means the rate-determining step isn’t the sluggish and energy-intensive nitrogen dissociation.
‘The activation energy of ammonia synthesis was the lowest among many reports so far,’ says Hosono. LaCoSi’s secret is a curious ‘hot atom’ mechanism: the energy released during adsorption of nitrogen on the catalyst’s surface helps break the triple bond.
‘Comparatively, the catalyst reported in this work may not be as efficient as the iron- and ruthenium-based catalysts used in industry, albeit it outperforms some of the cobalt-based catalysts,’ says Ping Chen, an expert in low-temperature ammonia synthesis at the Chinese Academy of Sciences. ‘I’m anxious to see if there are any real showstoppers, either with regards to synthesis or scale-up or compatibility with current systems,’ adds University of Michigan, US, chemical engineer Levi Thompson.
Nevertheless, Thompson calls Hosono and Wang’s work ‘pretty exciting’. ‘Tackling low temperature ammonia synthesis is one of those holy grails of chemistry,’ he says. The Tokyo scientists are now working on larger scale experiments, for which they need to improve the catalyst’s surface area.
‘It’s a very interesting piece of work in a very important area that is becoming increasingly topical,’ agrees Justin Hargreaves, catalytic materials researcher at the University of Glasgow, UK. ‘With the increasing availability of renewable sources of hydrogen, there is a desire to generate ammonia on more localised scales, for example for local fertiliser production or for energy storage,’ he adds. ‘I think [this study] will stimulate more activity.’

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Monday, 15 January 2018

QUITING CIGARETTE: Enzyme removes nicotine from blood

Image result for nicotine
NICOTINE

Scientists in the US have engineered an enzyme that halts nicotine’s psychoactive effects by breaking it down in the blood, before it can reach the brain. The enzyme could be developed into a nicotine dependence treatment that smokers could take to help them stop smoking. 
Quitting smoking is hard. A US government report from 2011 found almost 70% of American smokers want to quit and over half of smokers have tried to quit but fewer than 6% succeeded. Current cessation treatments and prescription medicines to help people stop smoking have varying success rates. Clinical trials of vaccines that encourage the body to develop nicotine antibodies to prevent it from crossing the blood–brain barrier failed to increase abstinence rates compared to a placebo.
An alternative to blocking nicotine is breaking it down. Back in 2015, K D Janda and colleagues at the Scripps Research Institute reported that the microorganism Pseudomonas putida has an enzyme, NicA2, which catalyses the oxidation of nicotine to N-methylmyosmine. In vivo tests with the enzyme had promising results but on moving to in vitro tests it became apparent the kidneys would filter out NicA2, rendering any treatment with the free enzyme short-lived.
Now, Janda and his team have stabilised NicA2. Crystal data showed that the first 52 amino acids of NicA2 are uninvolved in its activity so the team removed 50 of those and fused the rest of the enzyme to an albumin-binding domain. Associating NicA2 with albumin – the most abundant protein in plasma – increased its half-life in the body.
The team tested their new treatment on nicotine-addicted rats. After 24–48 hours of abstinence, the rats treated with the modified enzyme were less irritable and experienced fewer withdrawal symptoms, such as tremors and teeth chattering, than those who had not. The enzyme also completely eliminated nicotine from the rat’s blood and broke it down into harmless non-psychoactive products.
‘Helping smokers quit by depriving them of the nicotine kick through a nicotine degrading enzyme circulating in the body is certainly an interesting approach’ says Per-Åke Nygren, an expert in protein biotechnology at the KTH Royal Institute of Technology in Sweden. ‘However, the anti-drug immunological response from repeated delivery of a nicotine degrading enzyme of bacterial origin needs to be assessed. There is a risk that patients might develop neutralising antibodies, or that other adverse effects arise.’
Janda says this proof of concept provides a glimpse that biological products may have a role in treating substance use disorders. He adds ‘we will optimise the system to enhance further stability in vivo and remove potential parts that could cause an immune response.’

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BENZONITRILE identified in interstellar space


Image result for BENZONITRILE

The aromatic molecule benzonitrile has been detected in the Taurus Molecular Cloud – a region of interstellar space known for containing complex molecules – using radio telescopes.
Aromatic molecules are thought to be widely distributed throughout the universe, responsible for as-yet unidentified infrared bands – emissions generated by numerous cosmic sources. This, however, is the first time a specific aromatic molecule has been detected using radio spectroscopy.
Scientists at the National Radio Astronomy Observatory in Charlottesville, Virginia, used a method called spectral stacking to hunt through existing radio emissions data – gathered by the Nobeyama radio telescope in Japan – for a number of simple aromatic molecules, including benzonitrile. They were able to confirm the molecule’s identity using their own experimental data measuring the different rotational transitions of benzonitrile, combined with more observations from the Green Bank Telescope in West Virginia, which detected nine different rotational transitions of benzonitrile in the same region.
Their findings offer insights into the formation of more complex organic molecules in this part of space, where material will eventually be incorporated into new stars and planets.

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Friday, 1 December 2017

DISCOVERY: BENZENE ALKYLATION DISOBEY 'LIKE REPEL LIKE' RULE WITH CALCIUM

A calcium compound that allows electron-rich benzene to react with an electron-rich reagent – and thereby defy chemical logic – has been discovered by chemists working with alkyl calcium complexes

‘The appeal of the reaction is that it breaks the rules,’ says Michael Hill from the University of Bath, UK, who made the discovery together with his PhD student Andrew Wilson and computational chemist Laurent Maron from Paul Sabatier University in Toulouse, France.
For chemists, the concept ‘like repels like’ means that electron-rich molecules like benzene can hardly be convinced to react with nucleophiles. To make alkyl-substituted benzenes, the Friedel–Crafts alkylation therefore uses an electrophile, with which the aromatic ring readily reacts. However, the 140-year-old reaction has two major shortcomings: it cannot attach linear alkanes to the aromatic ring and it tends to produce a mixture of compounds because the product of the first alkylation reacts further.
Hill’s calcium-mediated nucleophilic alkylation overcomes these limitations. ‘[The calcium complex] sets benzene up for the nucleophilic attack and it also drags electron density away from that electron-rich aromatic ring,’ Hill explains. It then transfers its alkyl substituent to benzene and removes the superfluous hydrogen atom from the ring, producing a benzene with a linear alkane chains such as ethylbenzene.
‘It’s very beautiful chemistry,’ says main-group organometallic chemistry expert Eva Hevia, from the University of Strathclyde, UK. ‘It’s the type of paper I’ll talk about with my final year undergraduate students to show them how we should be open-minded about what metals can do and that we can’t take for granted what the textbooks tell us.’
THE DISCOVERY 

Discovering calcium’s rule-breaking behaviour was complete coincidence, says Hill. Wilson was investigating the reaction between calcium hydride and terminal alkenes to produce alkyl calcium complexes. But the reaction was slow. He decided to heat it to 60°C to speed it up. The reaction produced alkylbenzenes – an unexpected result.
‘We recognised was that we were forming the alkylated benzene from the reaction between the alkyl calcium and the reaction solvent, benzene,’ Hill explains. ‘The observation that this may be a nucleophilic attack was very provocative.’ Maron and his team analysed the reaction computationally, confirming Hill’s hunch.
Although Hill admits that the reaction currently might be of limited use for organic synthesis – it requires a stoichiometric amount of the air-sensitive calcium complex – calcium might offer more surprises. ‘These compounds have a much wider reactivity than we reported so far,’ he tells Chemistry World.
‘Now it’s down to synthetic chemists to expand the scope of this kind of methodology and see if it can be applied to other aromatic molecules like toluene and naphthalene,’ adds Hevia. ‘The potential is vast.’

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Tuesday, 24 October 2017

COMPUTER RECONSTRUCTION: MICROSCOPY GETS 100-FOLD PRECISION BOOST

S
Sharpening an image using the reconstruction-based Peri method enhances the precision of confocal microscopy. The original data can be seen in the left half of the image and the reconstruction in the right
Cornell University, US, scientists have devised a way to overcome frustrations researchers can face with high resolution microscopy techniques that aren’t precise enough. Itai Cohen and James Sethna’s teams boost colloid image precision 10–100-fold in under a day, by comparing images with computer reconstructions costing around $0.10 (£0.08) an hour to run. The approach is ‘a universal method of scientific image analysis that extracts all the useful information theoretically contained in a complex image’, the Cornell teams claim.
The researchers developed the parameter extraction from reconstructing images (Peri) method after struggling to track spherical colloid particle movement. Although using confocal microscopy provided sufficient resolution to see the small particles they were interested in, poor precision meant the researchers were uncertain about their size and position.
To maximise precision, Cohen’s student Brian Leahy, who specialises in microscopy, worked with Sethna’s student Matthew Bierbaum, a theoretician. To identify the origins of the imprecision and find ways to describe and reconstruct them mathematically they had to ‘pound their brains heroically’, according to Cohen.
The team realised that comparing reconstructed and experimental images could improve particle position and size measurements. They could subtract the values recorded in the image from those produced by the reconstruction to see if they disagree, and tweak the reconstruction to minimise disagreement.
Bierbaum and Leahy had to search carefully through all the problems that might affect the image, selecting only those that are truly important to precise measurements. For example, they discarded the effect of particles moving while the microscope scanned across their sample because they found it was smaller than the precision level they could theoretically reach.
But the PhD researchers did find that aberrations in the microscope’s lens that cause light shining on the sample to blur in a ‘point spread function’ were important. So too were imperfections in distribution of the fluorescent dye mixed into the sample, stripes in the illuminating light itself and background noise. Leahy and Bierbaum then devised individual mathematical reconstructions of the problems, each one taking on a starkly different formulae.

Phenomenal value


The images in the resulting reconstructions involve 10 million pixels and 6000 variables, including the three-dimensional co-ordinates of every particle in the sample. And to study their sample in detail, they needed to reconstruct thousands of images. That may sound fearsome, but Cohen says that laying the groundwork is the hard part, while the image processing that follows becomes routine. It requires up to a day of computer time on a combination of Cornell computers and an Amazon cloud mainframe, costing a few dollars, to analyse each image. ‘That’s trivial for modern-day laboratories, and then to increase precision by a 100-fold, that’s really phenomenal,’ Cohen enthuses.
Peri enabled the Cornell scientists to measure colloid particles’ radii, which had been very difficult, down to nanometre precision, Cohen adds. They were therefore able to confirm values of an electrostatic potential acting between the particles on these nanometre scales. However, the implications are much broader. ‘You could think about doing this with any microscope,’ Cohen stresses.
Harvard’s Vinothan Manoharan agrees that Peri is broadly applicable, but notes that it would need to be modified, potentially substantially. One of its strengths is that it requires many fewer choices about how to clean-up images than existing processing techniques, he adds. ‘That simplifies the process, and it makes the results less sensitive to the particular choices of the person doing the analysis, which is important for reproducibility,’ Manoharan says.
Klaas Wynne from the University of Glasgow, UK, observes that Peri is not as significant an invention as techniques that have enabled scientists to pick out features below the diffraction limit. It does extract the maximum amount of information possible, but doesn’t increase the resolution of the image, he stresses.
Leahy is now applying the technique to transmission electron microscopes in Manoharan’s team, and Sethna’s group is looking at superconducting quantum interference device microscopy. Meanwhile, Cohen’s group is ‘applying these techniques like crazy to colloidal suspensions’. The scientists have also made their reconstruction code available open source, so other confocal microscopists can apply it. ‘It’s going to take some tinkering for people to apply this to their own microscopes,’ Cohen says, ‘but it’s basically done.’

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Tuesday, 17 October 2017

CHEMISTS: NOT INNOVATIVE ENOUGH

"We see that 80% of chemists are to some extent dissatisfied with the direction they feel they’re being pointed towards in their research" Tim Hoctor, Elsevier

A survey carried out by Reaxys, Elsevier’s web-based chemical data retrieval tool, suggests that chemistry has an innovation problem when compared with other disciplines, and that this may be harming its ability to attract and retain talented scientists.
Reaxys polled 186 chemists from across academia and industry, 78% of whom said they thought potential chemists chose to go into other sciences because the research seemed more ‘newsworthy’. Just over three-quarters of the survey respondents said there is a long-standing or growing problem in terms of attracting new talent to the subject, and 80% said innovation was being held back by an overemphasis placed on applied research.
‘A huge number of the researchers [we asked] are feeling stifled because they feel their science is being directed objectively for a goal […] there is a relentless focus on applications,’ says Elsevier’s Tim Hoctor. He says the survey was carried out because ‘it’s always been important to stay current with what is perceived in the field’. He adds that he was ‘not necessarily surprised’ by the survey responses because they echoed trends that Reaxys had identified previously.
‘It almost looks as though chemistry is at a point where it needs to acknowledge it must change,’ he says. ‘We see that 80% of chemists [we asked] are to some extent dissatisfied with the direction they feel they’re being pointed towards in their research. Almost 80% of the chemists [we asked] believe that there are other fields that are more newsworthy, and the majority of respondents think it will be difficult to attract people continuing in chemistry in the long term future.’
To address these ‘image problems’, he says, chemists need to focus on highlighting the ways in which research is cutting-edge and innovative in order to draw more people into the field. ‘There needs to be a change of recognition in what a chemist is and does. Fifty years ago chemists were seen in a wet lab over a burner. The chemists of today are technology first,’ he says.
He adds that this was recognised in the survey, with 84% of participants acknowledging that being ‘technologically savvy’ – requiring computational or data analysis skills – was crucial or very important for career progression.
Lee Cronin from Glasgow University in the UK, who has long championed the adoption of new digital technologies in chemistry, says the idea that chemists aren’t innovating is ‘nonsense’. ‘It’s just that a lot of people don’t understand what innovation in chemistry looks like today,’ he says. ‘It’s really a very sophisticated subject and communicating that innovation to people is hard.’
‘People should be reminded that chemistry does cure disease, keep the world fed and provides us with an increasingly clean environment… There is a way to communicate that better and a way to collaborate better and that’s what I think digital tools may give. And those digital tools will then address the misconceptions that chemists aren’t trained or tech-savvy enough.’
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EBOLA: PAPER TEST DIAGNOSIS UNVEILED

To combat deadly outbreaks of Ebola, researchers need a variety of simple, portable tests that help them control and treat infections. N...