These findings could also be of interest for biotechnology. With the knowledge that autotrophic organisms using this "backward cycle" depend on the CO₂ concentration, scientists can apply it to more efficiently convert substrates into value-added products.
The scientists wanted to understand what factor determines whether the citric acid cycle runs "forwards" or "backwards" in the bacteria. Cultivating the bacteria under different conditions, they noticed that the growth of these organisms was highly dependent on the CO₂ concentration in the gas phase. In detail, the high CO₂ concentration was needed to allow the function of another important enzyme, pyruvate synthase. This enzyme is responsible for assembling acetyl coenzyme A (acetyl-CoA), the product of the "reversed cycle." The high CO₂ concentration drives the pyruvate synthase reaction in the direction of carboxylation and the entire cycle backwards, enabling CO₂ to be converted into biomass. The studied Hippea maritima and Desulfurella acetivorans were able to grow very well at 20% and 40% CO₂ in the gas phase but only moderately at 5% CO₂, and no growth was possible at 2% or 1% CO₂. As a control, the scientists studied another autotrophic bacterium Desulfobacter hydrogenophilus , which uses the energetically more expensive ATP-citrate lyase version of the reversed citric acid cycle. In this bacterium, growth was not affected by the CO₂ concentration.
The "backward cycle" that uses citrate synthase for citrate cleavage cannot be bioinformatically predicted, as it does not have the key enzymes whose presence can be used as a marker for the functioning of the pathway. Therefore, as an identifying feature for bioinformatic analyzes, the scientists used the detected high levels of citrate synthase in these bacteria's protein cocktail. Using a special analysis tool, the researchers were able to predict the production levels of individual proteins. With this trick, it was possible to predict the functioning of the "backward cycle" for inorganic carbon fixation in many anaerobic bacteria.
The scientists also showed that no gene regulation was necessary for switching from the oxidative ("forward") to the reductive ("reverse") direction. "This means that the cells can react very quickly on the availability of the carbon source in the environment" says Ivan Berg. "They use either the reductive direction to fix CO₂, if the concentration of CO₂ is high, or the oxidative direction, if another carbon source is available."
The methods used in the study were mass spectrometry and 13C-isotope analyses, enzyme measurements, protein quantification as well as media and amino acid analyses using chromatographic and spectrometric methods (LC/MS or GC/MS). With bioinformatic methods, they examined the occurrence of certain nucleotide base combinations (codons) in order to make predictions about the production of individual proteins.
Materials provided by University of Münster . Note: Content may be edited for style and length.
Halsey wears yellow wig and plunging psychedelic top in '60s makeover to promote new make-up
Halsey proved to be her own best advert on Thursday as she promoted her new About Face make-up range with a quirky 60s-inspired look.
The singer, 26, wowed as she sported a yellow wig, a plunging psychedelic top and striking eyeshadow as she celebrated the release of the newest collection from her brand, 'Daytripper'.
In a new video shared to her Instagram, Halsey mimed along to Nancy Sinatra's 1966 classic These Boots Are Made For Walking as she transformed herself from fresh-faced beauty to a dazzling 60's diva.
The Without Me hitmaker, who is currently pregnant, oozed confidence as she rocked the showstopping look, which included a cleavage-baring multicoloured top.
Her yellow tresses were gathered in a high ponytail, while she accessorised her attire with huge blue disk earrings.
Not surprisingly, her make-up was perfectly applied, with Halsey sporting eyeshadow in hues of yellow and green, with her eyes framed with a striking black trim.
Earlier this week, the star shared another flawless snap of herself in the same outfit as she shared her excitement about the release of the collection.
Shoppers love this £14 Amazon shirt can be easily dressed up or down | Daily Mail Online
The ZANZEA Women's Casual V-Neck Long Sleeve Loose Shirt currently stands as one of Amazon's bestselling Women's Blouses & Shirts
'Room for a thin top underneath if you want to cover up cleavage, and the sleeves can be worn up or down with securing buttons.
'Can be easily dressed up or down, creating different looks. Well impressed!! Got the black and turquoise ones so far! Wash brilliantly and quickly.'
It's lightweight, soft, hangs beautifully with a rounded hem, and has been designed with 3/4 length sleeves and a notch v-neck.
The minimalist blouse is a wardrobe essential, and it's versatile too, as it can be dressed up or down to suit your occasion.
Throw on high-waisted faux leather leggings and heels for a night out. Or pair with jeans and your favourite lockdown leggings while working from home. It can even be worn alone as a dress.
'I ordered a size bigger than usual and fits good I could have probably ordered usual size too as a tunic look. It's great. Def recommend - I've now ordered two more in diff colours.'
'Easy to wash and wear,' raved another. 'Comfortable and light. Great value, and it's long enough for a tall person. Lovely blue gets lots of great comments.'
Biomass production by reverse citric acid cycle | Mirage News
A research team from the University of Münster and the Technical University of Munich (TUM) has gained new insights into the citric acid cycle: At very high carbon dioxide concentrations, bacteria can also use this central metabolic pathway “backwards” to build useful compounds from carbon dioxide using the enzyme citrate synthase. It is possible that these findings can also be used biotechnologically.
But, under anaerobic conditions, in the absence of oxygen, some bacteria can perform the cycle in reverse order: They can build up biomass from CO₂. In this so-called reversed citric acid cycle, citrate synthase is replaced by ATP-citrate lyase, which consumes cells’ universal energy carrier adenosine triphosphate (ATP) to cleave citrate instead of forming it.
However, a few years ago, a research team led by Ivan Berg (University of Münster) and Wolfgang Eisenreich (Technical University of Munich) discovered that instead of requiring ATP-citrate lyase for the reversed cycle, some anaerobic bacteria can use citrate synthase itself to catalyze citrate cleavage – without consuming ATP.
A main question of their current research was, what factor determines whether the citric acid cycle runs “forwards” or “backwards” in the bacteria. Cultivating the bacteria under different conditions, they noticed that the growth of these organisms was highly dependent on the CO₂ concentration in the gas phase.
The studied Hippea maritima and Desulfurella acetivorans were able to grow very well at 20% and 40% CO₂ in the gas phase but only moderately at 5% CO₂, and no growth was possible at 2% or 1% CO₂. As a control, the scientists studied another autotrophic bacterium Desulfobacter hydrogenophilus, which uses the energetically more expensive ATP-citrate lyase version of the reversed citric acid cycle. In this bacterium, growth was not affected by the CO₂ concentration.
The high CO₂ concentration was needed to allow the function of another important enzyme, pyruvate synthase. This enzyme is responsible for assembling acetyl coenzyme A (acetyl-CoA), the product of the “reversed cycle”. The high CO₂ concentration drives the pyruvate synthase reaction in the direction of carboxylation and the entire cycle backwards, enabling CO₂ to be converted into biomass.
The “backward cycle” that uses citrate synthase for citrate cleavage cannot be bioinformatically predicted, as it does not have the key enzymes whose presence can be used as a marker for the functioning of the pathway. Therefore, as an identifying feature for bioinformatic analyzes, the scientists used the detected high levels of citrate synthase in these bacteria’s protein cocktail.
Using a special analysis tool, the researchers were able to predict the production levels of individual proteins. With this trick, it was possible to predict the functioning of the “backward cycle” for inorganic carbon fixation in many anaerobic bacteria.
The scientists also showed that no gene regulation was necessary for switching from the oxidative (“forward”) to the reductive (“reverse”) direction. “This means that the cells can react very quickly on the availability of the carbon source in the environment” says Ivan Berg. “They use either the reductive direction to fix CO₂, if the concentration of CO₂ is high, or the oxidative direction, if another carbon source is available.”
Ayala Pharmaceuticals Inc.
AL102 is an oral small molecule that inhibits gamma secretase. Inhibition of gamma secretase prevents the cleavage and shedding of BCMA, which are ubiquitously expressed on MM cells. Preclinical data have demonstrated that treatment with AL102 increases expression of membrane-bound BCMA on the surface of MM cells and could enhance activity of WVT078.
The Phase 1, open-label, multicenter trial of AL102 in combination with Novartis' WVT078 is currently enrolling patients with relapsed and/or refractory multiple myeloma who have received two or more standard of care lines of therapy including an IMID, a proteasome inhibitor, and an anti-CD38 agent. The first-in-human dose escalation trial is designed to assess the safety, tolerability and recommended dose regimen(s) of WVT078 alone and in combination with AL102. In addition, the trial will assess preliminary anti-MM response and characterize the pharmacokinetics and immunogenicity of WVT078 alone and in combination with AL102.
Under the terms of the option and license agreement established in December 2018, Novartis is responsible for the conduct and expenses of any trials of AL102 in combination with their BCMA-targeting agents, as well as potential commercialization, in multiple myeloma. Ayala retains worldwide license rights to AL102 in all other indications.
About AL102 AL102 is a potent, selective and oral gamma secretase inhibitor (GSI). AL102 is currently being developed for the treatment of desmoid tumors, as well as in combination with Novartis' BCMA-targeting agents for the treatment of multiple myeloma (MM).
About WVT078 WVT078 is a bispecific antibody that engages both BCMA and CD3, resulting in the recruitment of cytotoxic T cells that target BCMA-positive MM cells.
Receive full access to all new and archived articles, unlimited portfolio tracking, e-mail alerts, custom newswires and RSS feeds - and more!
Novocure Announces FDA IDE Approval and Steering Committee for KEYNOTE-B36 Trial Evaluating Tumor
"In vivo data suggest that using TTFields together with anti-PD-1 therapy results in increased tumor response versus either therapy alone," said Asaf Danziger, Novocure's Chief Executive Officer. "We are honored to have such an esteemed group of key opinion leaders join the KEYNOTE-B36 steering committee as we look to translate our preclinical knowledge into clinical data demonstrating the effect of TTFields together with pembrolizumab in first-line NSCLC. With the FDA IDE approval, we are now working closely with trial sites, investigators and institutional review boards to open sites and enroll patients as quickly as possible."
Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a broad range of clinical trials across all phases, included four phase 3 pivotal trials in a variety of tumor types. To date, more than 18,000 patients have been treated with TTFields.
In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Novocure's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, clinical trial progress, development of potential products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, coverage, collections from third-party payers and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Novocure's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, environmental, regulatory and political conditions as well as issues arising from the COVID-19 pandemic and other more specific risks and uncertainties facing Novocure such as those set forth in its Annual Report on Form 10-K filed on February 25, 2021 with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Novocure does not intend to update publicly any forward-looking statement, except as required by law. Any forward-looking statements herein speak only as of the date hereof. The Private Securities Litigation Reform Act of 1995 permits this discussion.
Receive full access to all new and archived articles, unlimited portfolio tracking, e-mail alerts, custom newswires and RSS feeds - and more!
The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and
Dylan McDermott Is Disturbingly Sexy in New Law & Order: Organized Crime Sneak Peek
The clip starts off with Gina making her way down to Richard's exclusive and incredibly private wine cellar. Before long, she's joined by Richard, who gives the undercover detective a fright.
"If you find him, bring him back upstairs," Richard responds. "I'm gonna grab a bottle of champagne."
As Gina expresses her interest in the wine cellar, Richard invites her inside the private space. While taking in the elaborate wine cellar, Richard boasts that it's his design. He adds, "I'll admit, I'm proud of it."
When Richard turns his back, Gina pulls a bug from her cleavage. Yet, before she can plant it, Richard turns his attention back on Gina.
"I was gonna study architecture," he says with a steely look. "Then, my first year at Columbia, I had this idea how technology could make healthcare more available to millions of disenfranchised people."
"I don't understand math at all," she responds still in character. "It just doesn't compute for me."
"No, no don't," Richard comments in a voice that's both sensual and unsettling. "I'm pretty sure that you could do just about anything if you put your mind to it."
With her back to Richard, Gina reveals she'd "really like to be a wine expert." In reality, she is taking this moment to successfully plant the listening device in Richard's wine cellar.
"I'll tell you what, next time you come over, we'll have a lesson," a potentially suspicious Richard concludes. "But right now, we should get back upstairs and celebrate Richie."
No comments:
Post a Comment