Lab reproduction of a marine compound with antibiotic properties

Public release date: 20-Jun-2013
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Contact: Sonia Armengou
armengou@irbbarcelona.org
34-934-037-255
Institute for Research in Biomedicine (IRB Barcelona)

This news release is available in Spanish.

Bacterial resistance to drugs leads pharmaceutical labs to be in constant search for new antibiotics to treat the same diseases. For the last thirty years, the sea bottom has yielded a wealth of substances with properties of interest to the pharmaceutical industry. Isolated from a marine microorganism off the coast of Alicante by the company BioMar, baringolin shows promising antibiotic activity at a very low concentration. The Combinatorial Lab headed by Fernando Albericio at the Institute for Research in Biomedicine (IRB Barcelona), which collaborates with BioMar, has now synthesized this molecule and revealed its structure. Today's results open up the possibility to better understand how this substance works and to design derivatives to turn into a viable drug in the next 10 years. These findings are advanced in todays' online edition of Angewandte Chemie, the scientific journal of reference in chemistry.

The researcher Xavier Just-Baringo, who is doing his PhD in the Combinatorial Chemistry Lab, has spent the last four years studying the structural composition of baringolin and has reconstructed this molecule in the lab as if it were 3D a puzzle of atoms that can be joined up in many ways. "This substance has 128 possible structural configurations but only one is an exact replica of the natural peptide. We have been able to find it via 39 synthesis steps," explains Just-Baringo who has had the privilege to name the new compound.

The researchers have finely tuned the organic synthesis of the natural peptide and several analogues and will address the biological activity of these molecules and attempt to improve their pharmacological and pharmacokinetic properties. Through collaboration with the Department of Pharmacology at the Hospital Clnic de Barcelona, they will test the analogues against several strains of gram-positive bacteria, one of the two large groups into which bacteria are classified and against which baringolin has shown inhibitory activity.

Thiopeptides: a new family of antibiotics

Structurally speaking, baringolin is a thiopeptide. These molecules are a new family of antibacterial agents of terrestrial and marine origin, and about 100 have been identified to date. "There is only one thiopeptide on the market for the treatment of bacterial infections, thiostrepton (Panolog), and it is used in veterinary medicine for skin infections. Nothing is available for humans yet," explanis Mercedes lvarez, associate researcher in the lab, senior professor at the University of Barcelona (UB), and supervisor of the study. The main drawback of thiopeptides is that they show low solubility. For baringolin to be viable as a drug, its solubility must be improved because antibiotics are administered orally or intravenously. "Using the analogues, we aim to improve this feature and identify the parts of the molecule responsible for their antibiotic activity in order to be able to design new more active and smaller analogues," says lvarez.

"We have taken the first step towards achieving a future drug," says Albericio. "Along the way we have learnt how to synthesize natural molecules and have developed new methods," adds the head of the group and senior professor at the UB. The final objective of the lab is to achieve the total synthesis of natural substances, the last two of which have been thiocoralin, an antitumoral agent that belongs to PharmaMar, and baringolin, belonging to BioMar. "The synthesis of natural products in the lab has a double justification. One is environmental, to protect species that hold substances of pharmacological interest, and the other is commercial, as manufacturing a drug on a large scale is viable only if its production can be ensured on an industrial scale," explain the researchers.

###

Reference article:

Total Synthesis and Stereochemical Assignment of Baringolin
Xavier Just-Baringo, Paolo Bruno, Lars K. Ottesen, Librada M. Caedo, Fernando Albericio and Mercedes lvarez. Angewandte Chemie (2013) http://dx.doi.org/10.1002/ange.201302372 (German Edition)
http://dx.doi.org/10.1002/anie.201302372 (International Edition)

---

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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.

Public release date: 20-Jun-2013
[ | E-mail | Share ]

Contact: Sonia Armengou
armengou@irbbarcelona.org
34-934-037-255
Institute for Research in Biomedicine (IRB Barcelona)

This news release is available in Spanish.

Bacterial resistance to drugs leads pharmaceutical labs to be in constant search for new antibiotics to treat the same diseases. For the last thirty years, the sea bottom has yielded a wealth of substances with properties of interest to the pharmaceutical industry. Isolated from a marine microorganism off the coast of Alicante by the company BioMar, baringolin shows promising antibiotic activity at a very low concentration. The Combinatorial Lab headed by Fernando Albericio at the Institute for Research in Biomedicine (IRB Barcelona), which collaborates with BioMar, has now synthesized this molecule and revealed its structure. Today's results open up the possibility to better understand how this substance works and to design derivatives to turn into a viable drug in the next 10 years. These findings are advanced in todays' online edition of Angewandte Chemie, the scientific journal of reference in chemistry.

The researcher Xavier Just-Baringo, who is doing his PhD in the Combinatorial Chemistry Lab, has spent the last four years studying the structural composition of baringolin and has reconstructed this molecule in the lab as if it were 3D a puzzle of atoms that can be joined up in many ways. "This substance has 128 possible structural configurations but only one is an exact replica of the natural peptide. We have been able to find it via 39 synthesis steps," explains Just-Baringo who has had the privilege to name the new compound.

The researchers have finely tuned the organic synthesis of the natural peptide and several analogues and will address the biological activity of these molecules and attempt to improve their pharmacological and pharmacokinetic properties. Through collaboration with the Department of Pharmacology at the Hospital Clnic de Barcelona, they will test the analogues against several strains of gram-positive bacteria, one of the two large groups into which bacteria are classified and against which baringolin has shown inhibitory activity.

Thiopeptides: a new family of antibiotics

Structurally speaking, baringolin is a thiopeptide. These molecules are a new family of antibacterial agents of terrestrial and marine origin, and about 100 have been identified to date. "There is only one thiopeptide on the market for the treatment of bacterial infections, thiostrepton (Panolog), and it is used in veterinary medicine for skin infections. Nothing is available for humans yet," explanis Mercedes lvarez, associate researcher in the lab, senior professor at the University of Barcelona (UB), and supervisor of the study. The main drawback of thiopeptides is that they show low solubility. For baringolin to be viable as a drug, its solubility must be improved because antibiotics are administered orally or intravenously. "Using the analogues, we aim to improve this feature and identify the parts of the molecule responsible for their antibiotic activity in order to be able to design new more active and smaller analogues," says lvarez.

"We have taken the first step towards achieving a future drug," says Albericio. "Along the way we have learnt how to synthesize natural molecules and have developed new methods," adds the head of the group and senior professor at the UB. The final objective of the lab is to achieve the total synthesis of natural substances, the last two of which have been thiocoralin, an antitumoral agent that belongs to PharmaMar, and baringolin, belonging to BioMar. "The synthesis of natural products in the lab has a double justification. One is environmental, to protect species that hold substances of pharmacological interest, and the other is commercial, as manufacturing a drug on a large scale is viable only if its production can be ensured on an industrial scale," explain the researchers.

###

Reference article:

Total Synthesis and Stereochemical Assignment of Baringolin
Xavier Just-Baringo, Paolo Bruno, Lars K. Ottesen, Librada M. Caedo, Fernando Albericio and Mercedes lvarez. Angewandte Chemie (2013) http://dx.doi.org/10.1002/ange.201302372 (German Edition)
http://dx.doi.org/10.1002/anie.201302372 (International Edition)

---

[ | E-mail | Share ]

?

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.

Source: http://www.eurekalert.org/pub_releases/2013-06/ifri-lro062013.php

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Movie Review: ?Man of Steel? Is Appropriately Super | njtoday.net ...

3 & ? popcorns

By Michael S. Goldberger,?film critic

Dear reader, before I tell you how much I enjoyed director Zack Snyder?s ?Man of Steel,? let me save you a few bucks. Skip the 3-D version. Virtually ineffectual, I suspect whatever afterthought process they employed proved a Kryptonite to the film?s color quality. That noted, be aware that I have never been so sure that Superman indeed exists.

Embodied in appearance and moral stature by handsome Henry Cavill, the origins and lore of the title character are entertainingly retold, thrillingly reminding us why we?ve become so enamored of the famous American legend in the first place. He showcases it with aplomb: X-ray vision, great feats of strength and, oh my, the flying was never better.

It may be a bit of an oxymoron, but the comic book hero created in 1933 by high school students Jerry Siegel and Joe Shuster now gets his most realistic interpretation, and yet happily doesn?t relinquish the great fantasy and hope that shape the core of his essence. Most of all, he is good, a beacon of honesty and compassion that can sure comfort a kid.

As this latest exploit unfolded, I joyfully remembered poring over the avalanche of back issue D.C. Comics in Norman Ginsberg?s basement, surely the greatest such repository in the Western World. Doubtless, today its contents would rival civilization?s great fortunes. We?d read and read, occasionally interjecting with supposition, inquiry and pontification.

Of greater ecstasy, though, which this film permutation reminds of most, was getting the very latest issue of Superman when it arrived at Krupman?s candy store (Krupmans large and small lived in the back). It was a dime. You could get two Hershey bars for that. And it felt thin, not yet transformed to the eternally thumbed-through heft of its predecessors.

Nonetheless, this early acquaintance with extravagance was exhilarating. I rubbed my palm across the sleek cover, held it up to smell its freshness before imbibing, and then hesitated yet another moment, as if saving a special morsel on my dinner plate for last?knowing that the sooner I started, the sooner all this great preciousness would end.

Thus, I posit, director Snyder and Mr. Cavill?s newest Superman manage to tell not only the glory of one who could give all the world?s evildoers a good what for, but also make that personal connection to us. There is an extra touch of class behooving the superhero emeritus, the one who would instate the genre and pave the way for all other superheroes.

Moving to and fro across the time continuum, from Superman?s birth on the dying planet of Krypton, where scientist dad Jor-El (Russell Crowe) launches baby Kal-El to his date with destiny on Earth, to his current exploits, Mr. Snyder weaves his tale well. Metaphors
and references smartly set up the flashbacks and fast forwards, and populate the scenario.

But, just to be sure it also pleases those who couldn?t care less about any of that legacy stuff, ?Man of Steel? doesn?t take a backseat to any FX extravaganza on the big screen today. Krypton exile General Zod, as worthy a villain as Superman is a savior, isn?t very happy about Kal-El?s smuggled departure. This makes for galactic battle scenes galore.

Played by Michael Shannon, the Machiavellian general, a colleague of Jor-El?s before Krypton?s sad fate caused a difference of opinion, is into the super stuff, too, as in super race and Krypton ?ber alles. For complex DNA reasons having to do with a MacGuffin known as the Codex, his imperialistic aims require Superman be extricated from Earth.

Hence, though the screenplay nicely iterates all the trials and tribulations of growing up with and learning to handle one?s extraordinary powers?which I?m sure we can all relate to?Zod?s incursion represents Superman?s trial by fire. Exhilarating, it smartly mixes with heady polemical ruminations about the eternal war between democracy and fascism.

And, lest we forget many an American adolescent?s earliest encounter with romance, Amy Adams?s winsome yet gutsy Lois Lane vibrantly enters stage right. Nicely woven into the fabric of what is essentially an allegory about immigration and attitudes thereof, she?ll ensure that the super refugee is familiarized with our real national pastime.

Among other personae vital to Superman?s education, Russell Crowe is strong as his biological dad; Diane Lane and Kevin Costner are touching as Smallville?s Ma and Pa Kent, respectively; and, teaching our man that what doesn?t kill you makes you stronger, alluring Antje Traue is a force to be contended with as Zod?s henchwoman, Faora-Ul.

This all makes for a fine time at the Bijou, but not just because of the adventure or clever scripting. It?s the iconically American subtext. While we have no equivalent of the Iliad to extol our ethos save for patriot Joel Barlow?s (1754-1812) never popularly embraced ?Vision of Columbus,? ?Man of Steel? gloriously and intelligently celebrates our mettle.
?
?Man of Steel,? rated PG-13, is a Warner Bros. release directed by Zack Snyder and stars Henry Cavill, Amy Adams and Michael Shannon. Running time: 143 minutes

Source: http://njtoday.net/2013/06/20/movie-review-man-of-steel-is-appropriately-super/

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Chemical that makes naked mole rats cancer-proof discovered

June 19, 2013 ? Two researchers at the University of Rochester have discovered the chemical that makes naked mole rats cancer-proof.

The findings could eventually lead to new cancer treatments in people, said study authors Andrei Seluanov and Vera Gorbunova. Their research paper will be published this week in the journal Nature.

Naked mole rats are small, hairless, subterranean rodents that have never been known to get cancer, despite having a 30-year lifespan. The research group led by Seluanov and Gorbunova discovered that these rodents are protected from cancer because their tissues are very rich with high molecular weight hyaluronan (HMW-HA).

The biologists' focus on HMW-HA began after they noticed that a gooey substance in the naked mole rat culture was clogging the vacuum pumps and tubing. They also observed that, unlike the naked mole rat culture, other media containing cells from humans, mice, and guinea pigs were not viscous.

"We needed to understand what the goo was," said Seluanov.

Gorbunova and Seluanov identified the substance as HMW-HA, which caused them to test its possible role in naked mole rat's cancer resistance.

Seluanov and Gorbunova then showed that when HMW-HA was removed, the cells became susceptible to tumors, confirming that the chemical did play a role in making naked mole rats cancer-proof. The Rochester team also identified the gene, named HAS2, responsible for making HMW-HA in the naked mole rat. Surprisingly, the naked mole rat gene was different from HAS2 in all other animals. In addition the naked mole rats were very slow at recycling HMW-HA, which contributed to the accumulation of the chemical in the animals' tissues.

The next step will be to test the effectiveness of HMW-HA in mice. If that test goes well, Seluanov and Gorbunova hope to try the chemical on human cells. "There's indirect evidence that HMW-HA would work in people," said Seluanov. "It's used in anti-wrinkle injections and to relieve pain from arthritis in knee joints, without any adverse effects. Our hope is that it can also induce an anti-cancer response."

"A lot of cancer research focuses on animals that are prone to cancer," said Gorbunova. "We think it's possible to learn strategies for preventing tumors by studying animals that are cancer-proof."

Previous research by Seluanov and Gorbunova showed that the p16 gene in naked mole rats stopped the proliferation of cells when too many of them crowd together. In their latest work, the two biologists identified HMW-HA as the chemical that activates the anti-cancer response of the p16 gene.

The research was supported by grants from the U.S. National Institutes of Health and the Ellison Medical Foundation.

Hyaluronan (HA), which makes tissues supple and aids in the healing process, is found in high concentrations in the skin of naked mole rats. The biologists speculate that the rodents developed higher levels of HA in their skin to accommodate life in underground tunnels.

Future research from the Gorbunova and Seluanov labs will focus on determining whether the HMW-HA from naked mole rats may have clinical value for either treating or preventing cancer in humans.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_environment/~3/FIw5xovQ4GI/130619132444.htm

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94th Military Police Company Take on the Dismounted Patrol Lane at Golden Coyote

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94th Military Police Company take on the dismounted patrol lane at Golden Coyote. Army Staff Sgt. Tyson Hensley, observer controller/trainer for the dismounted patrol lane for Golden Coyote, and Joint Force Headquarters of South Dakota, and a Hill City S.D. Resident. Available in High Definition.

This work, 94th Military Police Company Take on the Dismounted Patrol Lane at Golden Coyote, by SGT Matthew Keeler, identified by DVIDS, is free of known copyright restrictions under U.S. copyright law.

Source: http://www.dvidshub.net/video/294063/94th-military-police-company-take-dismounted-patrol-lane-golden-coyote

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Botox Treatments Toxic Injection Inside Of Fashion To Young Girls

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Source: http://www.articlesnatch.com/Article/Botox-Treatments-Toxic-Injection-Inside-Of-Fashion-To-Young-Girls/5078639

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Business Sales Associate by FlexiROAM - Your Part Time Sdn. Bhd ...

Your Part Time Sdn. Bhd. - Selangor , Damansara Perdana, Selangor, Malaysia

Job Description

Job Responsibilities:?

?

-Present and customize sales script of services, in order to persuade potential distributors/ business partner to better target the needs and interests of specific individuals.?

-Contact businesses or private individuals by telephone in order to solicit sales for product or services/ secure appointments (cold calling) and follow up closely on assigned leads.?

-Build network and maintain effective relationship with potential customers from sources such as events, fair, telephone directories, magazine reply cards and name cards to consolidate a solid customer database.?

-Address customer enquiry and propose appropriate solutions to customer patiently to effectively close sales.?

-Manage sales cycle from order to payment and delivery by obtaining customer information and travel details Monitor distribution channels/ sales account performances to ensure transactions are active and follow up on pending payments.?

-Participate in promotional events or road shows, work with developers, advertisers to market products or services that suites the specific distributors. Assist Sales team to generate quotation, proposals, invoice on ad-hoc basis.?

-Prepare sales report whenever requested for management to facilitate decision making.?

?

?

Job Requirement

Job Requirements:?

?

-At least 2 year(s) of working experience specializing in Sales - Corporate or equivalent.?

-Candidate must possess at least a Diploma, Advanced/Higher/Graduate Diploma, Bachelor's Degree, Post Graduate Diploma, Professional Degree, any field.?

-Able to communicate effectively and is driven by challenge?

Required language(s): Bahasa Malaysia, Chinese, English?

-2 Full-Time position(s) available.?

?

Salary Range:?

RM2,500 (Basic Salary + Phone Allowance) + Attractive Incentive + Travel Claim?

?

Working Location :?

Damansara Perdana,Petaling Jaya?

?

JOB REQUIREMENT

Years Of Experience : 1 Year

Age Range : 20-35

Salary Range : RM 2500 Monthly

Nationality : Malaysian

Race : Any

Gender : Both

Job Start From : 18-06-2013

?

If interested,please send your resume to tania@yourparttime.com with email title "Business Sales Associate".For more information,please do contact Ms Tania at 016-3669471 .?

?

Thank you in advance for your application and good luck.

Company Description

YourPartTime.com is an online service to match freelancers or part-time job seekers with employers who have part-time jobs. We strive to assist employers to human resource needs, particularly part-time and freelance workforce.

We have recently re-branded our site to "Your One-stop Talent Search Solution" where we promise to bring some best talents in the country at your convenience. We have divided the talent category to (i) Online Talent and (ii) Talent Placement.

Online talent (OT) focuses on online or Internet talents. These talents can be found online (an online resume/portfolio available or is easily reachable on the Internet) and they can work either online or offline. Some examples of the popular online talent can be found in the education/training category like copywriters, freelance writers, and translators. Other popular ones can be found in IT Freelance/Computer/Designer category like graphic designer, programmer, and 3D animators. Other than that, data entry, insurance agents, tele-marketers, surveyors and affiliate marketing consultants can be considered online talents.

Talent placement (TP) focuses on offline or on-ground talents. These talents can be found online or offline but they must be able to work offline/on-the-ground. Some examples of the popular offline talent can be found in the Marketing/Sales/Events category like promoters, sales consultant, and event producer. Other popular ones can be found Hotel/Restaurant/F&B category like waiters, ushers, outdoor functions and chef. Other than that, make-up artist, health consultant, driver, clown and receptionist can be considered offline talents.

With passion and experience through a dedicated team, we aim to solve your most pressing challenges day in and day out on part-timer/freelance recruitment.

Source: http://www.jenjobs.com/jobs/jobdetails/1016203/236074

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Maine MLTI schools overwhelmingly choose Apple over mandated HP

?

Apple asserts 92 percent dominance in Maine school orders

When Maine schools were given the choice for the first time under the next school year's Maine Learning Technology Initiative (MLTI) between Windows-based laptops, the Apple iPad, and the Apple MacBook Air, the schools overwhelmingly chose Apple products. Of 69,059 hardware orders placed, 92 percent of the purchases will come from Apple.

While 100 percent of Maine's schools have not chimed in with orders, 39,457 students and educators will start using the iPad at a cost of $266 per year, per seat with associated network expenses according to the Maine Department of Education. The MacBook Air has been adopted by 24,128 students and staff at $319 per year with networking, $33 above the funding provided by the state. A distant third is Governor Paul R. LePage's preferred option, the HP ProBook 4440 laptop running Windows 7 at $286 per seat with associated network expenses included.

Most of Maine's Career and Technical education centers have not placed orders, but less than 8,000 machines remain to be ordered. The final order totals will be submitted by the state on June 24, with teacher devices in hand in July. Student devices are scheduled to arrive before the start of the school year.

"These devices put students in the driver?s seat," Education Commissioner Stephen Bowen said. "Modern educational software adjusts to each child in ways that a teacher cannot, providing increased instruction on a concept where students need it, and less when they don?t. The result is an educational system in Maine that is truly able to meet the needs of all students as it best prepares them for college and career in an increasingly digital world."

Governor LePage said of the HP offer that it was "important that our students are using technology that they will see and use in the workplace. The laptops use an operating system that is commonly used in the workplace in Maine. This is the lowest-priced proposal, and these laptops will provide students with the opportunity to enhance their learning and give them experience on the same technology and software they will see in their future careers."

By Electronista Staff

Source: http://electronista.feedsportal.com/c/34342/f/626172/s/2d884df2/l/0L0Selectronista0N0Carticles0C130C0A60C190Capple0Basserts0B920Bpercent0Bdominance0Bin0Bmaine0Bschool0Borders0C/story01.htm

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