Study creates bacteria that consume carbon dioxide for growth

Agencies
November 30, 2019

Washington D.C., Nov 30: Researchers have developed bacteria called Escherichia coli, which consume carbon-di-oxide for energy instead of organic compounds.

This creation in synthetic biology highlights the incredible plasticity of bacterial metabolism and could provide the framework for future carbon-neutral bioproduction. The work appeared in the journal -- Cell.

"Our main aim was to create a convenient scientific platform that could enhance CO2 fixation, which can help address challenges related to the sustainable production of food and fuels and global warming caused by CO2 emissions," said senior author Ron Milo, at systems biologist at the Weizmann Institute of Science.

"Converting the carbon source of E. coli, the workhorse of biotechnology, from organic carbon into CO2 is a major step towards establishing such a platform," added Milo.

A grand challenge in synthetic biology has been to generate synthetic autotrophy within a model heterotrophic organism.

Despite widespread interest in renewable energy storage and more sustainable food production, past efforts to engineer industrially relevant heterotrophic model organisms to use CO2 as the sole carbon source has failed.

Previous attempts to establish autocatalytic CO2 fixation cycles in model heterotrophs always required the addition of multi-carbon organic compounds to achieve stable growth.

"From a basic scientific perspective, we wanted to see if such a major transformation in the diet of bacteria -- from dependence on sugar to the synthesis of all their biomass from CO2 -- is possible," said first author Shmuel Gleizer (@GleizerShmuel), a Weizmann Institute of Science postdoctoral fellow.

"Beyond testing the feasibility of such a transformation in the lab, we wanted to know how extreme an adaptation is needed in terms of the changes to the bacterial DNA blueprint," added Gleizer.

The researchers used metabolic rewiring and lab evolution to convert E. coli into autotrophs. The engineered strain harvests energy from formate, which can be produced electrochemically from renewable sources.

Because formate is an organic one-carbon compound that does not serve as a carbon source for E. coli growth, it does not support heterotrophic pathways.

They inactivated central enzymes involved in heterotrophic growth, rendering the bacteria more dependent on autotrophic pathways for growth.

They also grew the cells in chemostats with a limited supply of the sugar xylose -- a source of organic carbon -- to inhibit heterotrophic pathways.

The initial supply of xylose for approximately 300 days was necessary to support enough cell proliferation to kick start evolution. The chemostat also contained plenty of formates and a 10% CO2 atmosphere.

By sequencing the genome and plasmids of the evolved autotrophic cells, the researchers discovered that as few as 11 mutations were acquired through the evolutionary process in the chemostat.
One set of mutations affected genes encoding enzymes linked to the carbon fixation cycle.

The authors said that one major study limitation is that the consumption of formate by bacteria releases more CO2 than is consumed through carbon fixation.

In addition, more research is needed before it's possible to discuss the scalability of the approach for industrial use.

In future work, the researchers will aim to supply energy through renewable electricity to address the problem of CO2 release, determine whether ambient atmospheric conditions could support autotrophy, and try to narrow down the most relevant mutations for autotrophic growth.

"This feat is a powerful proof of concept that opens up a new exciting prospect of using engineered bacteria to transform products we regard as waste into fuel, food or other compounds of interest," Milo said.

"It can also serve as a platform to better understand and improve the molecular machines that are the basis of food production for humanity and thus help in the future to increase yields in agriculture," added Milo.

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Dr G K Sudhakar Reddy
August 4,2020

Being overweight or obese is now recognised as a serious cause of ill health and disability. There is a significant positive association between orthopaedic disorders and the level of obesity causing pain, deformity and difficulty in walking.

Excess body weight accumulation increases pressure on joints, particularly the hips, knees and ankles.

Here are a few type of  arthritis:

Osteoarthritis

It is a condition of damage/ wear and tear of the joint lining or cartilage. Obesity triggers this by loading excessive weight on the weight bearing joints like the knee and the hip. 

Knee Osteoarthritis

This is the most common arthritis especially in the Indian subcontinent.

While walking, an individual exerts 3 to 6 times pressure that of the body weight on the weight-bearing knee joint, which means in an obese with excess body weight, larger forces are exerted, which lead to higher risk of deterioration of cartilage.

In addition, there are excessive fat tissues that produce hormones and other factors that affect the joint cartilage metabolism and cause inflammation of the joints giving rise to joint pathology.  Leptin is one of the hormones causing knee osteoarthritis. 

Hip osteoarthritis

The force exerted across the hip is 3 times that of body weight. Hip osteoarthritis is caused by factors such as joint injury, increasing age and being overweight.    

Hand osteoarthritis

The observation that obese individual has a higher risk in having hand osteoarthritis has led to a hypothesis that the metabolic effect produced by fat tissue is the underlying factor. 

Osteoporosis

It is a progressive bone condition of decrease in bone mass and density (Bone Mineral Density or BMD) which can lead to an increased risk of fracture. Recent research suggests that obesity may accelerate bone loss. It is the amount of muscle mass which is seen in an active person, which accounts for bone strengthening effects and not due to the fat seen in a heavy person.

Low back pain

Low back pain from degenerative disc disease of the lumbar spine is one of the most disabling conditions in the community and overweight and obesity have the strongest association with seeking care for low back pain.

Managing Hip and Knee Osteoarthritis

Life style changes

If one is overweight, try to lose weight by doing more physical activity and eating a healthier diet. Regular exercise keeps you active and mobile and builds up muscle, thereby strengthening the joints and can improve symptoms. 

Pain Killers

Painkillers help with pain and stiffness for short term. They don’t affect the arthritis itself and won’t repair the damage to your joint. Creams and gels can be applied directly onto painful joints.

Nutritional Supplements

Glucosamine and chondroitin are nutritional supplements. Animal studies have found that glucosamine can both delay the breakdown of and repair damaged cartilage. However, there is insufficient evidence to support the use of glucosamine in humans and one can expect only a mild-to-moderate reduction in pain

Joint injections

If pain from osteoarthritis is severe joint steroid injections are injected into the joints that can reduces swelling and pain. The injections can start working within a day or so and may improve pain for several weeks or months. 

Hyaluronic acid injections, which help to lubricate your knee joint also give short term relief. In early stages. Stem cell treatment or cartilage regeneration procedures are being tried in young people with small defects, however it is still experimental and lacks long term evidence.

Surgery

May be recommended if you have severe pain or mobility problems.

Arthroscopy

If one has frequent painful locking/stiffening episodes especially in the knee joint, an operation to wash out loose fragments of bone and other tissue as joint can be performed by a minimally invasive key hole procedure called Arthroscopy.

Arthrodesis

If hip or knee replacement is not suitable, especially in young people who do heavy manual work, one can consider an operation known as an arthrodesis, which fuses your joint in a permanent position. This means that your joint will be stronger and much less painful, although you will no longer be able to move it.

Osteotomy

In young, active people in whom a knee joint replacement would fail due to excessive use one can consider an operation called an osteotomy. This involves adding or removing a small section of bone either above or below your knee joint.  This helps realign your knee so your weight is no longer focused on the damaged part of your knee. An osteotomy can relieve your symptoms of osteoarthritis, although you may still need knee replacement surgery eventually as you grow old

Joint replacement surgery

Joint replacement therapy is most commonly carried out to replace hip and knee joints. It involves replacing a damaged, worn or diseased joint with an artificial joint made of special plastics and metal.

For most people, a replacement hip or knee will last for at least 20 years, especially if it is cared for properly and not put under too much strain.

Dr G K Sudhakar Reddy is a Sr Consultant Orthopaedic Surgeon at Citizens Speciality Hospitals, Hyderabad

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Agencies
February 24,2020

Singapore, Feb 24: Last week Singapore's Ministry of Trade and Industry revised their 2020 GDP growth projections downwards to -0.5 to 1.5 per cent, confirming fears of economic fallout from the coronavirus COVID-19. Just three days earlier, while visiting Changi Airport, the Prime Minister told the media that the country is bracing for a significant hit on the economy and the possibility of a recession.

In the budget announcement on February 18, various measures to help affected companies were announced.

This included a jobs support scheme to help companies retain workers that will see the government offset 8 per cent of wages up to SGD3,600(USD2,600) per worker, per month, for a three-month period. Companies will also get a 25 per cent rebate on their taxes for the year capped at SGD15,000 (USD10,800) per company.

There will be additional support for sectors directly affected by the virus outbreak such as tourism, aviation and retail. Qualifying companies will be given property tax rebates and can apply for temporary bridging loans to ease cash flow. Rebates will be offered on aircraft landing and parking charges as well as rental rebates for shops and cargo agents at Changi Airport.

Overall, the economic package will cost Singapore some USD 4.6 billion, well in excess of the USD 500 million some analysts had predicted. The resulting spending plan including the virus economic package will see a budget deficit of SGD 10.9 billion or 2.1 per cent of GDP, the highest since the Asian financial crisis of 1997.

It is hoped that with financial support, companies in Singapore will not only be able to ride through the current rough patch but be able to position themselves better to take off once the economic crisis brought upon by the contagion is over.

Which then are the Singapore companies that can potentially ride out the current storm and emerge stronger?

Aviation and hospitality firms are among those most impacted by the virus outbreak and Singapore Airlines (SIA) comes to mind. SIA is a well-run company but has seen its share price fall about 5.2 percent since the beginning of the year. In the short term, revenue and profits will no doubt be affected but it will recover in the long run.

Hospitality sector companies like Ascott Residence whose main sponsor is Capitaland, Southeast Asia's largest landlord, and CDL Hospitality, have seen 1.5 and 5.5 percent (respectively) shaved off their share prices since the start of the year.

In reporting financial results for the quarter which ended in December on February 14, Alibaba CEO Daniel Zhang said that due to the virus, they are seeing large changes in buying patterns. With widespread home confinement, there is a growing demand for delivery services including online food and grocery delivery, as well as office apps and streaming entertainment.

Similarly, in Singapore, with more people staying and working from home, the three main food delivery services, Grab Food, Foodpanda and Deliveroo, are doing roaring business. All three are privately held.

In late January, as the scale of the outbreak became more apparent, investors began pouring money into health-product firms in Asia that they think will benefit from the virus outbreak.

Bloomberg reported that when Chinese pharmaceutical companies like Da An Gene Co, Xilong Scientific and Shanghai Kehua Bio-Engineering said they have developed kits for detecting the virus, their stocks soared to hit the 10 per cent daily limit. Firms manufacturing protection gear and air-cleaning equipment climbed more than 10 per cent in Japan, while Malaysian rubber gloves producers climbed at least 5 per cent.

Naturally, many would view that pharmaceutical companies that have the technology and expertise to develop drugs to treat patients with the virus or are able to develop a vaccine, would stand to benefit from the coronavirus outbreak.

Firms like and Johnson & Johnson, Pfizer, MSD, GlaxoSmithKline (GSK) and Sanofi are the pharmaceutical behemoths that dominate the global vaccine market.

However, industry experts speaking to the BBC warned that a pot of gold is not necessarily waiting for any company that successfully develops a vaccine. Although the global vaccine market is expected to grow to USD60 billion this year, it is costly and time-consuming to develop and pass it through for use by the general public.

It is also unclear if Indian pharmaceutical firms will be able to benefit from the demand for medicines that can treat or prevent the virus.

India is the world's largest manufacturer of generic drugs and it supplies 20 percent of the world's drugs by volume. However, it sources 70 percent of its raw material from China. If supplies are disrupted beyond a month to a month and a half, they may see a slow-down in production. According to a CNN report, the companies that are most impacted by material shortages are GSK India, Pfizer (PFE) and Cipla. Other companies like Aurobindo Pharma, Cadila Healthcare and Sun Pharma are said to be carefully monitoring the situation.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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