New antidepressant target discovered

Northwestern Medicine scientists have shown how manipulating a novel target in the brain using gene therapy could lead to new treatments for depression.

The investigators showed decreasing a set of proteins called HCN channels reduced depression-like behavior in mice. If replicated in humans, the findings could inform fresh therapies for millions of patients who do not respond to existing treatments for depression.

"Drugs currently available for treating depression help most patients, but they stop working for some patients and don't work from the get-go for others," said senior author Dr. Dane Chetkovich, a professor of neurology and of physiology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neurologist. "There is a real need for new therapies to help patients desperate for alternatives to the available therapeutic options."

Drugs currently available for treating depression help most patients, but they don't work for others.

Most existing antidepressants affect mood and emotions by increasing levels of neurotransmitters called monoamines, namely serotonin, dopamine and norepinephrine. But the fact that these drugs are not effective for many patients suggests there are additional mechanisms underlying depression yet to be uncovered that could be targeted with new therapies.

In previous research, Chetkovich's lab and others showed those mechanisms might involve the hippocampus, a region of the brain important for learning, memory and emotional regulation. There, they saw changes to HCN channels, typically involved in controlling the electrical activity of cells in the heart and brain, also played a critical role in behaviors linked to depression.

In the new study, a group of Northwestern scientists led by Chetkovich took steps to translate that insight into a potential gene therapy using mouse models. The scientists surgically injected mice with a nontoxic virus engineered to express a gene that turns off HCN channel function in hippocampus neurons.

"When the HCN channels stopped working, the mice behaved as if they'd been given antidepressant medications," Chetkovich explained.

In contrast, increasing the function of HCN channels removed the antidepressant effect.

To measure depression-like behavior, the scientists measured how long mice would seek to escape an environment before giving up - a test commonly used by the pharmaceutical industry to screen compounds for effectiveness as antidepressants, including medications currently on the market.

"This work not only identifies a totally new treatment target for depression, it provides a detailed molecular description of the structures that need to be manipulated for it to act as an antidepressant and develops viral tools to do so," said Chetkovich, who is also director of Feinberg's Medical Scientist Training Program.

In future research, the scientists are focusing on adapting the viral gene therapy approach to human patients. They also have a grant from the National Institute of Mental Health to find small molecules that could be developed into oral medications to turn off HCN channels in the brain.

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EU referendum: UK science wakes up to new future

UK science will have to fight to make sure it is not an after-thought as Britain renegotiates its relationship with the EU, say research leaders.

The science establishment expressed its "disappointment" on Friday with the referendum's outcome.

It had been in the "remain" camp.

How will UK science be affected by Brexit?

The decision to leave the EU now means new structures will have to be put in place if the science sector is to continue to enjoy favourable access to the union's programmes and funding.

Jo Johnson, the minister for universities and science - an "in" supporter - was one of the first to react.

He took to Twitter in the early hours to say: "Big decision. Let's make it work."

Britain's science sector has done increasingly well out of the EU in recent years, receiving €8.8bn in research funding in 2007-2013 versus the €5.4bn it paid in over the same period. And UK-based scientists have won about a fifth of all the grants, in terms of value, from the top-tier programmes run by the European Research Council.

This funding flow-back has been described as being akin to having another Research Council to go with the seven national bodies that presently distribute UK government monies.

To maintain access to the EU stream, Britain will likely now have to get itself some kind of "associated country" status, similar to the positions held by other non-EU countries such as Norway, Switzerland and Israel.

Associated countries pay a GDP membership fee to "join the club", after which, in principle, their scientists can bid for support in the same way as those from full EU member states.

But the exact arrangements will need to be worked out, and are going to depend on wider economic and political factors.

Switzerland, for example, only has "partial" associated status currently because it is not allowing Croatian citizens free access to its labour market.

And having free movement to work collaboratively is central to the way modern science is done.

Scientists for Britain is the group of researchers that has most prominently lobbied for Brexit.

It has argued that the policies of "political union" - and the regulations that flow from Brussels - are not a prerequisite for the UK playing a full role in European scientific collaborations.

The UK can survive and thrive outside full union membership, it contends.

And on Friday, its spokesman Dr Lee Upcraft said he was confident a new settlement would be found to maintain UK involvement in EU programmes and by extension the country's world-leading position in European and global science.

But he also urged the research establishment to hold government to account on national funding.

He echoed a recent complaint from Stephen Hawking, that "we've become reliant on EU funding. We get back a little more than we put in, and associated status will need to address this. But the other thing we need to do, and what UK academia needs to do, is get much better at lobbying government."

EU funding had masked a stagnation in national support, he told BBC News.

Dr Sarah Main from the neutral Campaign for Science and Engineering said there would inevitably be a big uncertainty factor going forward - which comes on top of sector changes already being pushed through parliament in the form of the Higher Education and Research bill (this will bring the seven Research Councils into a single body).

"In the run-up to the referendum, people talked a lot about associated status," she said. "To what extent the EU will make a clear path to enable the UK to obtain associated status and join science programmes back in the EU, I think will be driven by the politics.

"You have to remember that every associated country that people have quoted in the arguments up till now - none was previously a member of the EU that then exited. So, it won't necessarily be straightforward, but it would be welcome because we do want to compete in EU competitive funding streams, and as far as possible influence EU regulations, markets and the conditions for doing science and the training of scientists."

Prof Venki Ramakrishnan, the president of the Royal Society, agreed with Dr Main that ministers must not lose sight of science as they renegotiate Britain's relationship with the EU.

"In the upcoming negotiations, we must make sure that research, which is the bedrock of a sustainable economy, is not short-changed, and the government ensures that the overall funding level of science is maintained," he said in a statement.

Areas that should not be affected directly by the Brexit vote include the big intergovernmental research organisations.

The likes of the European Space agency; the European Southern Observatory, which operates major telescopes; and Cern, which runs the Large Hadron Collider, the largest cryogenic facility in the world at liquid helium temperature, are all separate legal entities to the EU.

However, EU money has increasingly been directed at some of their work. For example, Brussels is now the largest single contributor to Esa's budget, using the agency to procure the Galileo satellite navigation system and the Copernicus/Sentinel Earth observation constellation of satellites.

Britain's science-related companies working in these kinds of fields will want re-assurance that a renegotiated future does not turn into a competitive disadvantage.

Patrick Wood is the managing director of Surrey Satellite Technology Limited, which assembles the navigation payloads for every Galileo spacecraft.

He told BBC News on Friday: "We are days away from submitting the proposal for the next follow-on order, to complete the Galileo constellation, and we will continue to work hard with our supply chain to do this.

"I would look for our UK politicians to unite together to continue to support this flagship European project containing key UK technology, knowhow and to help protect jobs here in the UK."

Likewise, the chair of the House of Commons Science and Technology committee, Nicola Blackwood MP, wanted to highlight the care now needed to ensure the commercial science sector was properly supported.

"My committee's recent report into EU regulation of the life sciences pointed out that this sector alone comprises almost 5,000 companies employing 200,000 people in the UK, generating an annual turnover of £60bn. The Science and Technology Committee will want, in the coming weeks and months, to look at the consequences of this vote for British science," she said.

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Today in Chemistry History – Emil Erlenmeyer’s Birthday

The Erlenmeyer flask is a piece of glassware most of us have likely used at some point. The tapered sides and narrow neck of this flask allow the contents of the flask to be mixed by swirling, without risk of spillage, making them suitable for titrations. By placing it under the buret and adding solvent and the indicator in Erlenmeyer flask. Such features similarly make the flask suitable for boiling liquids. Hot vapors condense on the upper section of the Erlenmeyer flask, reducing solvent loss. Erlenmeyer flasks' narrow necks can also support filter funnels.

As Compound Interest notes “The Erlenmeyer flask’s popularity lies in its utility. Its flat base means it isn’t easily toppled, unlike the round-bottomed flasks which can also be found in the laboratory. Its tapered, cone-like shape, coupled with its narrow neck, means that liquids inside it can be swirled without spilling easily. Additionally, the sides minimise loss of liquids from the flask when they are heated, as vapours condense on the sides. The narrow neck can also be plugged with a rubber or glass stopper.”

Who was Erlenmeyer?

Erlenmeyer was the son of Dr. Friedrich Erlenmeyer, a Protestant theologian. He enrolled in the University of Giessen to study medicine, but after attending lectures of Justus von Liebig changed to chemistry. In the summer of 1846 he went to Heidelberg for one year, and studied physics, botany and mineralogy, returning to Giessen in 1847. After serving as assistant to H. Will and then to Carl Remigius Fresenius, Erlenmeyer decided to devote himself to pharmaceutical chemistry. For this purpose he studied in Nassau, where he passed the state pharmaceutical examination, and shortly afterwards acquired an apothecary’s business, first at Katzenelnbogen and then in Wiesbaden. He became dissatisfied with pharmacy and returned to chemistry, finishing his doctorate at Giessen in 1850.

In 1855 he moved to Heidelberg and there converted a shed into a private laboratory. In 1857 he became privatdocent and his habilitation thesis "On the manufacture of the artificial manure known as superphosphate” contained a description of several crystalline substances which greatly interested Robert Bunsen. It was while at Heidelberg that Erlenmeyer was brought under the influence of August Kekulé, whose theoretical views he was one of the first to adopt. He was the first to suggest, in 1862, that double and triple bonds could form between carbon atoms, and he made other important contributions to the development of theories of molecular structure.

In 1863 he became associate professor at the University of Heidelberg. In 1868 he was hired as full professor in Munich to take charge of the laboratories of the new Munich Polytechnic School, a post which he held until his retirement from teaching in 1883.

His work mostly focused on theoretical chemistry, where he suggested the formula for naphthalene and formulated the Erlenmeyer rule: alcohols in which the hydroxyl group is attached directly to a double-bonded carbon atom become aldehydes or ketones.

Erlenmeyer’s practical investigations were concerned mostly with aliphatic compounds. In 1859 he synthesised aminohexoic acid and proceeded to study the general behaviour of albuminoids on hydrolysis. He worked out methods to determine the relative amounts of leucine and tyrosine, which are produced during the degradation of several substances of this class, and was the first (1860) to understand the nature of glycide and to suggest that this substance is related to glycerol in the same way as is metaphosphoric acid to orthophosphoric acid. In the following year he studied the action of hydroiodic acid on glycerol, and showed that the product was isopropyl- and not propyl iodide. His investigations of the higher alcohols produced during fermentation yielded the important proof that these alcohols do not belong to the normal series.

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Ultra-thin slices of diamonds reveal geological processes

Diamonds are not only beautiful and valuable gems, they also contain information of the geological history. By using ultra-thin slices of diamonds, Dorrit E. Jacob and her colleagues from the Macquarie University in Australia and the University of Sydney found the first direct evidence for the formation of diamonds by a process known as redox freezing. In this process, carbonate melts crystallize to form diamond. The slices were prepared by Anja Schreiber of the GFZ German Research Centre for Geosciences in Potsdam, Germany. The work is published in Nature Communications. The study shows that the reduction of carbonate to diamond is balanced by the oxidation of iron sulphide to iron oxides.

Siberia's Udachnaya diamond mine, by Stepanovas (Stapanov Alexander). (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons

The researchers used the new nano-scale technique of Transmission Kikuchi Diffraction to discover rims of the iron oxide mineral magnetite just a few ten thousandths of a millimetre thick around sulphide minerals inside the diamonds. The GFZ's Anja Schreiber prepared these slices using a focussed beam of charged atoms (ions) to ablate the surface. The already ultra-thin slices were re-thinned after being mounted on a carbon-coated copper grid. This process was carried out for the first time successfully on a grid and yielded the data set used for the study.

The results also solve a puzzle that has occupied diamond researchers for decades, namely the over-abundance of sulphide occurring as inclusions in diamond. Iron sulphides are the most common inclusions in diamond even though there is only about 0.02% of sulphur in the mantle: it now appears that the oxidation of the iron sulphides directly causes the formation of the diamonds that include them.

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https://www.sciencedaily.com/releases/2016/06/160621115443.htm

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Dagger in Tutankhamun's tomb was made with iron from a meteorite

A dagger entombed with King Tutankhamun was made with iron from a meteorite, a new analysis on the metal composition shows.

In 1925, archaeologist Howard Carter found two daggers, one iron and one with a blade of gold, within the wrapping of the teenage king, who was mummified more than 3,300 years ago. The iron blade, which had a gold handle, rock crystal pommel and lily and jackal-decorated sheath, has puzzled researchers in the decades since Carter’s discovery: ironwork was rare in ancient Egypt, and the dagger’s metal had not rusted.

Italian and Egyptian researchers analysed the metal with an x-ray fluorescence spectrometer to determine its chemical composition, and found its high nickel content, along with its levels of cobalt, “strongly suggests an extraterrestrial origin”. They compared the composition with known meteorites within 2,000km around the Red Sea coast of Egypt, and found similar levels in one meteorite.

That meteorite, named Kharga, was found 150 miles (240km) west of Alexandria, at the seaport city of Mersa Matruh, which in the age of Alexander the Great – the fourth century BC – was known as Amunia.

The researchers published their findings on Tuesday in the journal Meteoritics & Planetary Science.

Although people have worked with copper, bronze and gold since 4,000BC, ironwork came much later, and was rare in ancient Egypt. In 2013, nine blackened iron beads, excavated from a cemetery near the Nile in northern Egypt, were found to have been beaten out of meteorite fragments, and also a nickel-iron alloy. The beads are far older than the young pharaoh, dating to 3,200BC.

“As the only two valuable iron artifacts from ancient Egypt so far accurately analysed are of meteoritic origin,” the team that studied the knife wrote, “we suggest that ancient Egyptians attributed great value to meteoritic iron for the production of fine ornamental or ceremonial objects”.

The researchers also stood with a hypothesis that ancient Egyptians placed great importance on rocks falling from the sky. They suggested that the finding of a meteorite-made dagger adds meaning to the use of the term “iron” in ancient texts, and noted around the 13th century BC, a term “literally translated as ‘iron of the sky’ came into use … to describe all types of iron”.

“Finally, somebody has managed to confirm what we always reasonably assumed,” Thilo Rehren, an archaeologist with University College London, told the Guardian.

Rehren, who studied the nine meteoritic beads, said “there never has been a reason to doubt this outcome but we were never really able to put this hard data behind it”.

He added that other objects from Tutankhamun’s tomb, including jewelry and miniature daggers, are believed to made from meteorite iron.

“Yes, the Egyptians referred to this stuff as metal from the heaven, which is purely descriptive,” he said. “What I find impressive is that they were capable of creating such delicate and well manufactured objects in a metal of which they didn’t have much experience.”

An iron meteorite, by James St. John (Flickr: Murnpeowie Meteorite) [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons

The researchers wrote in the new study: “The introduction of the new composite term suggests that the ancient Egyptians were aware that these rare chunks of iron fell from the sky already in the 13th [century] BCE, anticipating Western culture by more than two millennia.”

Egyptologist Joyce Tyldesley, of the University of Manchester, has similarly argued that ancient Egyptians would have revered celestial objects that had plunged to earth.

“The sky was very important to the ancient Egyptians,” she told Nature, apropos of her work on the meteoritic beads. “Something that falls from the sky is going to be considered as a gift from the gods.”

The high quality of the blade suggests that Tutankhamun, who lived during the latest stage of the Bronze Age, was supported by ironworkers who were skilled despite the relative rarity of the material.

The blade may not be the only item derived from falling rocks on Tut’s person.

In 2006, an Austrian astrochemist proposed that an unusual yellowish gem, shaped as a scarab in King Tut’s burial necklace, is actually glass formed in the heat of a meteorite crashing into sand.

“It would be very interesting to analyse more pre-Iron Age artifacts, such as other iron objects found in King Tut’s tomb,” Daniela Comelli, of the physics department at Milan Polytechnic, told Discovery News. “We could gain precious insights into metal working technologies in ancient Egypt and the Mediterranean.”

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http://www.theguardian.com/world/2016/jun/01/dagger-king-tut-tomb-iron-meteorite-egypt-mummy

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Rosetta’s comet contains ingredients for life

Ingredients crucial for the origin of life on Earth, including the simple amino acid glycine and phosphorus, key components of DNA and cell membranes, have been discovered at Comet 67P/Churyumov-Gerasimenko.

The possibility that water and organic molecules were brought to the early Earth through impacts of objects like asteroids and comets have long been the subject of important debate.

While Rosetta's ROSINA instrument already showed a significant difference in composition between Comet 67P/C-G's water and that of Earth, the same instrument has now shown that even if comets did not play as big a role in delivering water as once thought, they certainly had the potential to deliver life's ingredients.

ESA/Rosetta/NAVCAM, CC BY-SA IGO 3.0 [CC BY-SA 3.0-igo (http://creativecommons.org/licenses/by-sa/3.0-igo)], via Wikimedia Commons

While more than 140 different molecules have already been identified in the interstellar medium, amino acids could not be traced. However, hints of the amino acid glycine, a biologically important organic compound commonly found in proteins, were found during NASA's Stardust mission that flew by Comet Wild 2 in 2004, but terrestrial contamination of the collected dust samples during the analysis could not be ruled out. Now, for the first time, repeated detections at a comet have been confirmed by Rosetta in Comet 67P/C-G's fuzzy atmosphere, or coma.

The first detection was made in October 2014, while most measurements were taken during the perihelion in August 2015 - the closest point to the Sun along the comet's orbit while the outgassing was strongest. "This is the first unambiguous detection of glycine in the thin atmosphere of a comet," says Kathrin Altwegg, principal investigator of the ROSINA instrument at the Center of Space and Habitability of the University of Bern and lead author of the study. The results are now being published in Science.

Glycine is very hard to detect due to its non-reactive nature: it sublimates at slightly below 150°C, meaning that little is released as gas from the comet's surface or subsurface due to its cold temperatures. "We see a strong correlation of glycine to dust, suggesting that it is probably released from the grains' icy mantles once they have warmed up in the coma, perhaps together with other volatiles," says Altwegg. At the same time, the researchers also detected the organic molecules methylamine and ethylamine, which are precursors to forming glycine. Unlike other amino acids, glycine is the only one that has been shown to be able to form without liquid water. "The simultaneous presence of methylamine and ethylamine, and the correlation between dust and glycine, also hints at how the glycine was formed," says Altwegg.

Another exciting detection by ROSINA made for the first time at a comet is of phosphorus. It is a key element in all living organisms and is found in the structural framework of DNA and RNA.

"The multitude of organic molecules already identified by ROSINA, now joined by the exciting confirmation of fundamental ingredients like glycine and phosphorus, confirms our idea that comets have the potential to deliver key molecules for prebiotic chemistry," says Matt Taylor, Rosetta project scientist of the European Space Agency ESA. "Demonstrating that comets are reservoirs of primitive material in the Solar System, and vessels that could have transported these vital ingredients to Earth, is one of the key goals of the Rosetta mission, and we are delighted with this result."

Story Source:

The above post is reprinted from materials provided by University of Bern. Note: Materials may be edited for content and length.

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On this day in history - the moon landing goal was announced

In 1961, the formal announcement of an American lunar landing was made by President John F. Kennedy speaking to the Congress: “I believe that this nation should commit itself to achieving the goal, before this decade is out, of landing a man on the Moon and returning him safely to the Earth. No single space program in this period will be more impressive to mankind, or more important in the long-range exploration of space; and none will be so difficult or expensive to accomplish.” 

Since, a total of twelve men have landed on the Moon. This was accomplished with two US pilot-astronauts flying a Lunar Module on each of six NASA missions across a 41-month time span starting on 20 July 1969 UTC, with Neil Armstrong and Buzz Aldrin on Apollo 11, and ending on 14 December 1972 UTC with Gene Cernan and Jack Schmitt on Apollo 17. Cernan was the last to step off the lunar surface.

Lunar crater Daedalus on the Moon's far side

All Apollo lunar missions had a third crew member who remained on board the Command Module. The last three missions had a rover for increased mobility.

The atmosphere of the moon

The Moon has an atmosphere so tenuous as to be nearly vacuum, with a total mass of less than 10 metric tons (9.8 long tons; 11 short tons). The surface pressure of this small mass is around 3 × 10−15 atm (0.3 nPa); it varies with the lunar day. Its sources include outgassing and sputtering, the release of atoms from the bombardment of lunar soil by solar wind ions. Elements that have been detected include sodium and potassium, produced by sputtering, which are also found in the atmospheres of Mercury and Io; helium-4 and neon from the solar wind; and argon-40, radon-222, and polonium-210, outgassed after their creation by radioactive decay within the crust and mantle.

The absence of such neutral species (atoms or molecules) as oxygen, nitrogen, carbon, hydrogen and magnesium, which are present in the regolith, is not understood. Water vapour has been detected by Chandrayaan-1 and found to vary with latitude, with a maximum at ~60–70 degrees; it is possibly generated from the sublimation of water ice in the regolith. These gases can either return into the regolith due to the Moon's gravity or be lost to space, either through solar radiation pressure or, if they are ionized, by being swept away by the solar wind's magnetic field.

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