Brenntag builds on past successes with new CEO

 During the first annual general shareholders’ meeting since the successful IPO of Brenntag AG in March 2010, longtime CEO Stephen Clark handed over responsibility for the world market leader in chemical distribution to Steven Holland. Holland, who has been with Brenntag since 2006, has worked closely with Stephen Clark since becoming COO of the company in 2009. During this time he has been instrumental in shaping the strategy for Europe and Asia. As a new member of the Supervisory Board, longtime CEO Clark will support Brenntag in continuing the successful growth strategy. This was decided at the general shareholders’ meeting in Düsseldorf when the shareholders followed the proposal of major shareholder Brachem Acquisition S.C.A. In addition, the general shareholders’ meeting approved the distribution of a dividend of EUR 1.40 per share.

"It is with great confidence that I hand over responsibility for this successful and ambitious MDAX-company to my colleague Steven Holland", the outgoing CEO Stephen Clark said about his successor. "In recent years, Steven has proved to be a strong leader with strategic vision and has driven our growth with passion." Steven Holland has been a board member since 2007; he has been responsible for managing Brenntag’s global day-to-day operations and executing the group’s growth strategy since 2009.

The previous CEO Stephen Clark joins the Supervisory Board – a large majority of the voting shareholders decided in favour of a corresponding request of major shareholder Brachem Acquisition S.C.A. "Stephen Clark has further developed and expanded Brenntag’s global market leadership in chemical distribution with a great sense of responsibility. We highly appreciate and value his work and I would like to specifically thank Stephen Clark, also on behalf of the entire Supervisory Board, for this outstanding achievement. We look forward to continuing to benefit from his long standing know-how ", said Stefan Zuschke, Chairman of the Supervisory Board.

Clark hands over a growing company. Brenntag has significantly improved its results across all key performance indicators since the IPO last year. With EUR 7,649.1 million and EUR 602.6 million respectively, sales and operating EBITDA reached record figures. Based on these excellent results, the Management Board and the Supervisory Board proposed a dividend of EUR 1.40 per share to the general shareholders’ meeting. This corresponds to a total dividend of EUR 72.1 million. The shareholders approved this proposal by a large majority.

The shareholders welcomed the company's performance during the past financial year and adopted the proposals of the remaining agenda items with approval rates of almost one hundred percent.

The Brenntag management aims for further growth based on the good results of 2010. "The financial year 2011 is going well," said the new CEO Steven Holland. "We push ahead with our proven growth strategy and will consistently continue our expansion both organically and through acquisitions." Only in the past few weeks Brenntag has made successful strategic acquisitions in China and North America. On the back of global economic growth, continuing positive trends in chemical distribution and its strong international market position, Brenntag expects to further grow all key performance indicators in local currencies in the current financial year.

A possible fix for misfolding proteins

Troubled proteins in need of rescue may someday have a champion in a common drug used to treat high blood pressure.

The Rice University laboratory of bioengineer Laura Segatori reported today that research involving lacidipine, a calcium channel blocker also known by brand names Lacipil and Motens, could be a key to helping people who suffer from an incurable, neuropathic form of Gaucher disease. This inherited metabolic disorder is characterized by accumulations of a fatty substance in cells and certain organs that can prevent them from functioning properly. 

The paper by Segatori, Rice's T.N. Law Assistant Professor in Chemical and Biomolecular Engineering, and graduate student Fan Wang and Rice senior Ann Chou appears in today's online edition of Chemistry and Biology.

Segatori's research focuses on the misfolding of proteins, workhorses in the body that determine what cells and organs do and how they do it. Proteins start as chains of amino acids that snap in an instant into distinct configurations, a process that remains one of biology's great mysteries but one that Segatori and her peers are figuring out, bit by bit.

Proteins often misfold even in the healthiest persons, Segatori said, and cells have an elegant, efficient system for eliminating misfolded proteins and other refuse. But the system can break down.

In Gaucher disease, proteins containing destabilizing mutations misfold and are degraded very quickly. Loss of these proteins, which normally traffic to the lysosome and catalyze the degradation of lipids, results in buildup of these lipids; this can lead to such problems as a malfunctioning liver, enlarged spleen, skeletal disorders, anemia and neurological disorders. 

The Rice researchers worked with fibroblasts taken from skin lesions of people with Gaucher. They found that lacidipine enhances the protein-folding mechanism by modulating calcium levels and regulating the movement of signaling calcium ions. 

Segatori said impairment of calcium homeostasis further compromises the folding of already destabilized, mutated versions of the enzyme glucocerebrosidase (GC). Slowing the folding process ever so slightly by regulating calcium stabilizes GC and lets it fold properly and enter the lysosome, where it breaks down lipids. 

"If you can force the folding to occur, you can rescue native folding of mutant proteins, which has been shown to lead to restored activity," Segatori said.

Segatori and Wang hope their work opens the door to possible treatments for neuropathic diseases that will be easier on patients and less expensive than enzyme replacement therapy, which involves injecting recombinant protein. Segatori said lacidipine has three distinct advantages: It is nontoxic to cells, is a small molecule that readily crosses the blood/brain barrier and is approved for use in humans by the Food and Drug Administration.

On the other hand, the researchers have not yet studied the effect of lacidipine on neurons. "We don't want to say we can cure this disease with calcium blockers, but they are a good tool for research," Segatori said. "Essentially, we treat cells with this molecule and see if we rescued the protein activity. If we did, we can then work to understand what the molecule actually did to the folding machinery of the cell."

She also cautioned that calcium blockers might have side effects. "Their response in the cell is quite broad. That's why I'm hesitant to say that this could be a cure for Gaucher disease. Maybe we're rescuing the folding of that enzyme, but we don't know what else we might be doing." 

But the positive implications go beyond Gaucher. "There is possibly an avenue to use calcium blockers to further the study and treatment of other types of misfolding diseases," Segatori said. "Similar studies have been conducted using calcium blockers in neurons of Parkinson's patients. The results are highly promising. And there's also a lot of interest in the correlation between Parkinson's and Gaucher diseases, because it seems like a lot of people who have Gaucher are at risk for Parkinson's disease."

Gaucher disease occurs in about 1 in 50,000 to 1 in 100,000 people. Treatment for the more common types of the disease involves enzyme replacement therapy.

More information: Lacidipine Remodels Protein Folding and Ca2+ Homeostasis in Gaucher's Disease Fibroblasts: A Mechanism to Rescue Mutant Glucocerebrosidase, Chemistry & Biology, Volume 18, Issue 6, 766-776, 24 June 2011 DOI:10.1016/j.chembiol.2011.04.008

Abstract
The hallmark of Gaucher's disease cellular pathogenesis is the lysosomal accumulation of glucosylceramide, which is caused by misfolding of mutated glucocerebrosidase (GC) and loss of lysosomal GC activity, and leads to depletion of [Ca2+]ER. We demonstrate that modulation of Ca2+ homeostasis and enhancement of the cellular folding capacity synergize to rescue the folding of mutated GC variants. Lacidipine, an L-type Ca2+ channel blocker that also inhibits [Ca2+]ER efflux, enhances folding, trafficking, and activity of degradation-prone GC variants. Lacidipine remodels mutated GC proteostasis by simultaneously activating a series of distinct molecular mechanisms, namely modulation of Ca2+ homeostasis, upregulation of the ER chaperone BiP, and moderate induction of the unfolded protein response. However, unlike previously reported proteostasis regulators, lacidipine treatment is not cytotoxic but prevents apoptosis induction typically associated with sustained activation of the unfolded protein response.

Provided by Rice University (news : web)

Watching particles' jekyll-to-hyde transformation

Whether a common atmospheric particle stays in a stable form or twists into something else depends on the amount of water it encounters in the atmosphere, according to scientists at the University of Iowa and Pacific Northwest National Laboratory. This result for malonic acid challenges conventional wisdom; the results are based on the complementary experiments conducted at two Department of Energy user facilities in a collaborative project facilitated through PNNL's Chemical Imaging Initiative.

Managing today's fossil-fuel-based energy infrastructure for both economic and environmental health requires controlling the fate and transport of ubiquitous particles produced by combustion engines and other sources. Traditional approaches, which assume that the particles behave the same way in the air as they do in bulk aqueous solution, have created some faulty assumptions. The chemical imaging technique and subsequent study correct several of those assumptions, allowing scientists to work with more accurate, direct observations of these troublesome particles. This information could not have been obtained with conservative approaches.

"There were no means to probe in situ chemistry of individual particles as they take up water in the atmosphere," said Dr. Alexander Laskin, a chemist within PNNL's Chemical Imaging Initiative. "The X-ray spectro-microscopy technique allowed us to watch as the particles changed between the nonreactive and highly reactive forms."

It begins with malonic acid, one of the most abundant carboxylic acids in the atmosphere. This molecule exists in two forms called keto and enol that differ only with respect to the position of one of the hydrogen atoms. The two forms co-exist in equilibrium, and there is no physical or chemical way to separate these two forms.  With respect to their chemical reactivity, the keto form is stable and not very reactive, while the enol form is highly reactive. The common wisdom was that, in the atmosphere, the dominant form would be the keto form, the same as in aqueous solution. However, the team found that the aqueous chemistry results are not applicable in this case.

An abundant atmospheric species, malonic acid transforms from the stable, nonreactive keto form to the highly reactive enol form at elevated relative humidity. The reactive enol form is 4 to 5 orders of magnitude more abundant in the atmosphere than was expected from aqueous chemistry.

The team's approach began at EMSL, a DOE national scientific user facility at PNNL. Suman Ghorai and Prof. Alexei Tivanski of UI examined ensembles of malonic acid particles, characterizing hundreds of particles at a time using EMSL's optical microscopy and infrared spectroscopy techniques. "The experiments pointed out to unexpectedly high levels of the enol form, and allowed us to go to the light source with well-focused questions," said Ghorai, a graduate student who began the study at EMSL in 2009.

At the Advanced Light Source at Lawrence Berkeley National Laboratory, they probed individual particles using scanning transmission X-ray microscopy combined with near-edge X-ray absorption fine structure spectroscopy.

"Dr. Tivanski and his colleagues took a novel approach to the synchrotron based X-ray microscope," said Dr. Mary Gilles, an expert in the X-ray spectro-microscopy and a beam line scientist at the Advanced Light Source at LBNL. "Most people use it in static mode, but they did dynamic studies -- watching as the particles chemically changed in relation to the relative humidity."

Combining the light source and EMSL resources allowed the researchers to see the malonic acid molecules at the molecular level and determine which form was dominant. "The complementary capabilities were perfectly leveraged," said Tivanski, a UI professor who led the project. "It would have taken endless time at the synchrotron to come to the same results and conclusion if the EMSL part had not been available."

With the results from EMSL and ALS, the team determined that the highly reactive enol form is 4 to 5 orders of magnitude higher in particles than would be predicted from aqueous chemistry. "The implications could be very broad," said Laskin, EMSL scientist. "If you have more reactive enol intermediates, then many chemical reactions are triggered that you didn't expect."

What's next: "We saw the behavior in one carboxylic acid. Will we see it in others? That's the question we are planning to explore in future studies," said Laskin. The team and others will determine the answers using and refining the new chemical imaging approach.

More information: Ghorai S, A Laskin, and AV Tivanski. 2011. "Spectroscopic Evidence of Keto-Enol Tautomerism in Deliquesced Malonic Acid Particles." Journal of Physical Chemistry A 115, 4373-4380. DOI: 10.1021/jp112360x

Provided by Pacific Northwest National Laboratory (news : web)

Progress toward smell television: Targeted release of various scents from individually addressable chambers

 3-D movies, Dolby surround for a more realistic audio experience -- virtual reality is on the march. And how much more realistic would a film be if a barbecue actually smelled of grilled meat or if you could smell a sea breeze when the protagonist takes his love for an evening stroll on the beach? This type of smell experience may become reality for the home television viewer in the not-too-distant future.

In the journal Angewandte Chemie, a team led by Jongmin Kim at Samsung Electronics in Korea and Sungho Jin at the University of California, San Diego, USA, have now introduced a new approach for making a compact device that could fit on the back of a television to produce thousands of different scents.

Previous technologies for the controlled release of scents were not simple enough and were much too crude for the sensitive electronics of our televisions and video players. An odor module needs to be small and robust and deliver results that are reproducible over multiple cycles; the response should be rapid and the user should be able to regulate the strength of the odor. Kim, Jin, and their co-workers aim to overcome these challenges with their new concept.

Their method is based on an array of individual cells that are filled with scent-containing solutions. The miniature containers are made from a cross-linked silicone polymer. Except for a tiny hole in the top, they are completely sealed. A needle can be sued to inject a different scent solution into each cell. In the “off” state the tiny hole stays closed. The scent containers are switched on by heating. This causes the silicone to expand and the pressure on the inside to increase, forcing a small amount of gas-phase scent out of the tiny hole.

A two-dimensional lattice of heating wires, known as an X-Y matrix, can be used to specifically address individual containers. The scientists prepared a prototype, which they successfully tested with two different perfumes, “Live by Jenifer Lopez” and “Passion by Elizabeth Taylor”. Testers could detect both scents and differentiate between them.

“Our new concept is not only of interest for the entertainment industry,” state Kim and Jin, “it could also be used for combinatorial studies of gas-phase reactions and the development of vapor-based pharmaceuticals.”

More information: Sungho Jin, An X–Y Addressable Matrix Odor-Releasing System Using an On–Off Switchable Device, Angewandte Chemie International Edition, http://dx.doi.org/ … ie.201102759

Provided by Wiley (news : web)