Radical overhaul of farming could be ‘game-changer’ for global food security

Posted by Biomechanism

According to the authors of new research released today at the World Water Week in Stockholm, a radical transformation in how farming and natural systems interact could simultaneously boost food production and protect the environment—two goals that often have been at odds. The authors warn, however, that the world must act quickly if the goal is to save the Earth’s main breadbasket areas—where resources are so depleted the situation threatens to decimate global supplies of fresh water and cripple agricultural systems worldwide.

A new analysis resulting from the joined forces of the International Water Management Institute (IWMI) and the United Nations Environment Programme (UNEP) outlines the urgent need to rethink current strategies for intensifying agriculture, given that food production already accounts for 70 to 90 per cent of withdrawals from available water resources in some areas. The report, An Ecosystem Services Approach to Water and Food Security, finds that in many breadbaskets, including the plains of northern China, India’s Punjab and the Western United States, water limits are close to being “reached or breached.” Meanwhile, 1.6 billion people live under water scarcity conditions, and the report warns that the number could soon grow to 2 billion. The current situation in the Horn of Africa is a timely reminder of how vulnerable some regions are to famine“Agriculture is both a major cause and victim of ecosystem degradation,” said Eline Boelee of IWMI, the lead scientific editor of the report. “And whether we can continue increasing yields with the present practices is unclear. Sustainable intensification of agriculture is a priority for future food security, but we need to take a more holistic ‘landscape’ approach.”

Meanwhile, a separate report by IWMI, Wetlands, Agriculture and Poverty Reduction, warns against seeking to protect wetlands by simply excluding agriculture. It argues that policies focused entirely on wetland preservation and ignore the potential of ‘wetland agriculture’ to increase food production and contribute to reducing poverty.

“Blanket prohibitions against cultivation do not always reduce ecosystem destruction and can make things worse,” said Matthew McCartney of IWMI, who co-authored the report. “For example, sub-Saharan Africa's grassy ‘dambo’ wetlands often provide vital farmland to the rural poor. However, banning farming in these areas has exacerbated rather than reduced ecosystem destruction. It has prompted deforestation upstream and led to a shift from farming to grazing in the wetlands themselves, so there has been a much greater impact on these natural systems. A balance is needed: appropriate farming practices that support sustainable food production and protect ecosystems.”

New Alliance Between Agriculture and Environment Groups

The two reports seek a new path toward achieving food security and environmental health. They focus on radically reorienting practices and policies so that farming occurs in ‘agroecosystems’ that exist as part of the broader landscape, where they help maintain and supplement clean water, clean air and biodiversity.

“We are seeing a growing trend of alliances between traditionally conservationist groups and those concerned with agriculture,” said David Molden, Deputy Director General for Research at IWMI. UNEP is the United Nations' voice of the environment, and IWMI is part of the world’s largest consortium of agricultural researchers, the Consultative Group on International Agricultural Research (CGIAR).

“For instance,” Molden continued, “UNEP has adopted food security as a new strategic concern. IWMI and its partners in the CGIAR are developing a multi-million dollar research program that will look at water as an integral part of ecosystems to help solve issues of water scarcity and land and environmental degradation. IWMI has also recently become a key partner with the Ramsar Convention on the relationship between wetlands and agriculture.”

“The various political, research and community alliances now emerging are challenging the notion that we have to choose between food security and ecosystem health by making it clear that you can’t have one without the other,” he added.

Examples of Successful Integration in the Field

UNEP IWMI and collaborators have identified multiple opportunities to use trees on dryland farms that will intensify the amount of food produced per hectare of land area while helping to improve the surrounding ecosystem. Farmers can prevent runoff and soil erosion by integrating trees and hedgerows and retaining more water to nourish their crops.

Another example of innovative thinking includes better water and soil management in rainfed systems in sub-Saharan Africa, which have demonstrated the ability to reverse land degradation while increasing crop yields twofold or threefold at the same time.

Overall, the authors say it’s time for decision-makers at the international, national and local levels to embrace an agroecosystem approach to food production. These changes could include incentivising more farmers to adopt improved practices through ‘payments for environmental services (PES)’.

One example being explored by the CGIAR’s Challenge Program on Water and Food (CPWF) is the potential for benefit sharing in river basin areas of Peru, Ecuador and Colombia. Upstream users value the water for irrigation and ecotourism and have a spiritual affiliation with the ecosystem. The hydropower companies need a steady stream to support the downstream electrification of the growing urban population. Large-scale farms and agro-industry also need increasing supplies of water.

“More and more agriculture needs to be brought into the ‘green economy’,” said Alain Vidal of the CPWF. “We need to value farming practices that protect our precious water resources in the same way we are beginning to value forest management that helps reduce greenhouse gas emissions, especially because those natural resources support the livelihoods of the most vulnerable.”

In the report, An Ecosystem Services Approach to Water and Food Security, experts from UNEP, IWMI and 19 other organisations acknowledge that one major impediment to adopting a more sustainable approach to food production is that it requires a new level of cooperation and coordination among officials and organisations involved in agriculture, environmental issues, water management, forestry, fisheries and wildlife management—individuals and groups who routinely operate in separated, disconnected worlds.

“It is essential that in the future we do things differently. There is a need for a seminal shift in the way modern societies view water and ecosystems and the way we, people, interact with them,” said David Molden. “Managing water for food and ecosystems will bring great benefits, but there is no escaping the urgency of this situation. We are heading for disaster if we don’t change our practices from business as usual.”

Painting a ‘bullseye’ on cancer cells

Posted by Biomechanism 

“Targeting cancer cell metabolism can lead to more effective therapy, Tel Aviv University research finds.”

Scientists are constantly on the hunt for treatments that can selectively target cancer cells, leaving other cells in our bodies unharmed. Now, Prof. Eytan Ruppin of Tel Aviv University’s Blavatnik School of Computer Science and Sackler Faculty of Medicine and his colleagues Prof. Eyal Gottlieb of the Beatson Institute for Cancer Research in Glasgow, UK, and Dr. Tomer Shlomi of the Technion in Haifa have taken a big step forward. They have successfully created the first computerized genome-scale model of cancer cell metabolism, which can be used to predict which drugs are lethal to the function of a cancer cell’s metabolism.

By inhibiting their unique metabolic signatures, explains Prof. Ruppin, cancer cells can be killed off in a specific and selective manner. The efficacy of this method has been demonstrated in both computer and laboratory models pertaining to kidney cancer. Because the researchers’ new approach is generic, it holds promise for future investigations aimed at effective drug therapies for other types of cancer as well.

The results were recently published in the journal Nature.

Lethal to cancer, safe for other cells

The ability to specifically target cancer cells is the holy grail of cancer research. Currently, many cancer drugs are designed to target any proliferating cells in the body — and while cancer cells certainly proliferate, so do healthy cells, such as hair and gut lining cells, the growth of which are essential to the body’s overall health. This explains why many cancer treatments, including chemotherapy, have adverse side effects like nausea and hair loss.

Targeting the metabolism of the cancer cell itself may be one of the most effective ways forward. Cancer cells have a special way of metabolizing nutrients for growth and for energy. This makes cancer cell metabolism essentially different from that of a normal cell.

The researchers’ computer model is a reconstruction of the thousands of metabolic reactions that characterize cancer cells. By comparing it to a pre-existing model of a normal human cell’s metabolism, they could distinguish the differences between the two. They could then identify drug targets with the potential to affect the specific, special characteristics of cancer metabolism.

To test their predictions, the researchers chose to target cells from a specific type of renal cancer. “In this type of renal cancer, we predicted that using a drug that would specifically inhibit the enzyme HMOX, involved in Heme metabolism, would selectively and efficiently kill cancer cells, leaving normal cells intact,” explains Prof. Ruppin. Their computer model led them to hypothesize that the Heme pathway was essential for the cancer cell’s metabolism.

In an experimental study led by Prof. Gottlieb’s lab, the researchers were able to verify this prediction in both mouse and human cell models, and to study these metabolic alterations in depth.

An all-around treatment model

Metabolism is a large and complex network, built on thousands of reactions. It is beyond the human capability to fully understand, let alone predict how such a complicated system works, says Prof. Ruppin. Now, by allowing researchers to simulate the effects of a disorder, computer models are helping researchers to predict the efficacy of potential drugs and treatments. Though the predictions should always be verified in a lab or clinic, this method is highly cost effective and leads to exciting opportunities for accelerating future drug developments.

While the first model was built to characterize a specific type of cancer, this approach can be applied in the future for creating models for other types of cancer. “This is the next big challenge for us,” says Prof. Ruppin. “We are going to continue to build models for other types of cancer, and seek selective drug therapies to defeat them.” Their multidisciplinary approach requires both the predictions of a computer model and the findings of experimental clinical trials, and may lead to the faster development of more selective and effective cancer treatments.

At last, a reason why stress causes DNA damage

Posted by Biomechanism 

For years, researchers have published papers that associate chronic stress with chromosomal damage.

Now, researchers at Duke University Medical Center have discovered a mechanism that helps explain the stress response regarding DNA damage.

“We believe this paper is the first to propose a specific mechanism through which a hallmark of chronic stress, elevated adrenaline, could eventually cause DNA damage that is detectable,” said senior author Robert J. Lefkowitz, M.D., James B. Duke Professor of Medicine and Biochemistry and a Howard Hughes Medical Institute (HHMI) investigator at Duke University Medical Center.

The paper was published in the Aug. 21 online issue of Nature.

In the study, mice were infused with an adrenaline-like compound that works through a receptor called the beta adrenergic receptor Lefkowitz has studied for many years. The scientists found that this model of chronic stress triggered certain biological pathways that ultimately resulted in the accumulation of DNA damage.

“This could give us a plausible explanation of how chronic stress may lead to a variety of human conditions and disorders, which range from merely cosmetic, like greying hair, to life-threatening disorders like malignancies,” Lefkowitz said.

P53 is a tumour suppressor protein and is considered a “guardian of the genome” that prevents genomic abnormalities.

“The study showed that chronic stress leads to prolonged lowering of p53 levels,” said Makoto Hara, Ph.D., a postdoctoral fellow in the Lefkowitz laboratory. “We hypothesise that this is the reason for the chromosomal irregularities we found in these chronically stressed mice.”

Lefkowitz earlier had proved the existence of isolated, and characterized the G-protein-coupled receptors (GPCRs) such as the beta adrenergic receptor. These receptors, which are located on the surface of the membranes that surround cells, are the targets of almost half of the drugs on the market today, including beta blockers for heart disease, antihistamines and ulcer medications.

Now he is continuing studies along another pathway, stemming from the GPCRs, discovered in his lab, known as the beta-arrestin pathway. At first, the theory was that beta-arrestin proteins turned off or desensitized the G-protein pathways. Still, evidence is accumulating that these proteins are also responsible for causing certain biochemical activities in their own right.

In the current study, the scientists found a molecular mechanism through which adrenaline-like compounds acted through both G-protein and the beta-arrestin pathways to trigger DNA damage.

The Nature publication showed that the infusion of an adrenaline-like compound for four weeks in the mice caused degradation of p53, which was present in lower levels over time.

The study also showed that the DNA damage was prevented in mice lacking beta-arrestin 1. Loss of beta-arrestin 1 stabilized cellular levels of p53 both in the thymus, an organ that strongly responds to acute or chronic stress, and in the testes, where paternal stress might affect an offspring’s genome.

Future studies planned by the Lefkowitz laboratory include studying mice that are placed under stress (restrained), thus creating their own adrenaline or stress reaction to learn whether the physical reactions of stress, rather than an influx of adrenaline in the lab as was done in the current study, also leads to accumulation of DNA damage.

____________________

Other authors include Jeffrey J. Kovacs, Erin J. Whalen, Sudarshan Rajagopal, Ryan T. Strachan, Seungkirl Ahn, Barbara Williams, Christopher M. Lam, Kunhong Xiao, and Sudha K. Shenoy, all of the Duke Department of Medicine; Aaron J. Towers and Simon G. Gregory of the Department of Medicine and the Center for Human Genetics at Duke; and Wayne Grant and Derek R. Duckett of the Translational Research Institute, The Scripps Research Institute, Jupiter, Fla..

The study was supported by the Howard Hughes Medical Institute.

Newly discovered cell mechanism uses amplified nitric oxide to fight Clostridium difficile

Posted by Biomechanism

“Research involving Case Western Reserve featured in the Aug. 21 online issue of Nature Medicine.” 

Groundbreaking research encompassing Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, has uncovered a natural defense mechanism that is capable of inactivating the toxin that spreads Clostridium difficile, or C. diff, an increasingly common bacterial infection in hospitals and long-term care settings. The research has immediate implications for developing a new form of treatment for antibiotic-resistant bacteria.

People in good health usually don’t get C. difficile disease. You might get the disease if you have an illness that requires prolonged use of antibiotics. Increasingly, the disease can also be spread in the hospital. The elderly are also at risk. Treatment is usually with antibiotics.

The newly discovered mechanism involves a nitric oxide (NO)-based molecule, S-nitrosoglutathione (GSNO), which binds to the toxins secreted by C. diff  bacteria to deactivate them and prevent them from penetrating and damaging cells. The mechanism encompasses S-nitrosylation (SNO), a protein modification that attaches NO to cysteine residues in enzymes and other proteins.

“We’ve discovered a natural defense against C. diff that is based on nitric oxide, a ubiquitous molecule that is often produced by immune cells to kill pathogens,” says Jonathan Stamler, MD, director of the Institute for Transformative Molecular Medicine and the Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation at the Case Western Reserve University Cardiovascular Center and University Hospitals Harrington-McLaughlin Heart & Vascular Institute. “Understanding how this mechanism deactivates toxins provides a basis for developing new therapies that can target toxins directly and thereby keep bacterial infections, like C. diff, from spreading,” he says.

Dr. Stamler discovered the molecule GSNO, as well as the nitrosylation mechanism for control of protein function, in his previous research. He is one of the senior investigators studying how the protein modification inhibits the virulence of C. diff toxins. The resulting research findings appear in the Aug. 21 online issue of Nature Medicine.

In addition to Dr. Stamler, investigators from the University of Texas in Galveston, the University of California, Tufts University and the Commonwealth Medical College collaborated on the research. The University of Texas researchers first determined that NO helped protect cells against C. diff and approached Dr. Stamler to determine if SNO was also involved.

C. diff is the most common cause of hospital-acquired infectious diarrhea and life-threatening inflammation of the colon. It originates when normal, competing bacteria in the gastrointestinal tract are wiped out by the use of antibiotics. This allows C. diff bacteria to grow out of control.

The C. diff bacteria secrete a toxin that cleaves or cuts itself to generate a fragment that can penetrate cells, damaging them and resulting in a hemorrhagic injury to the gastrointestinal tract. The toxin is activated when inositolhexakisphosphate (InsP6), a substance prevalent in leafy vegetables and the gastrointestinal tract, binds to it, enabling the toxin to change shape and cleave itself.

The research shows that upon activation, GSNO, a NO donor molecule, binds to the toxin and nitrosylates it. This can only occur when InsP6 binds to the toxin.

The change in shape that results when InsP6 binds to the toxin is what enables the GSNO to target and inactivate the toxin by directly binding to the active site. There, the GSNO can nitrosylate (SNO) the cysteine to inactivate the toxin. These findings are especially significant as they suggest that GSNO has evolved to recognize shape changes in the toxins it targets.

Prior to this, researchers knew GSNO could produce SNO in many classes of proteins but there was little to no precedent for it binding to toxins or explaining how this SNO modification protects against infectious agents, Dr. Stamler says.

“The new research suggests GSNO, and S-nitrosylation, more generally, may have a universal function in protecting cells against microbial proteins, many of which have a design that is conducive to being s-nitrosylated by GSNO,” Dr. Stamler says. “In this regard, GSNO-like molecules may represent a new class of antibiotics that can be developed, exploiting the shape changes in numerous bacterial proteins.”

In their work, researchers also noted that increased levels of GSNO in the gut of C. diff-infected animals and increased levels of SNO-toxin in stools of patients, directly correlated with deactivation of the toxin, further confirming that the natural mechanism works to reduce disease activity in people. This provides a basis for measuring how much nitric oxide, a key molecule in cell immune activity, has bound to toxins to make SNO and limit the spread of bacteria.

The current treatment of C. diff is difficult and the infection often recurs. Resistance to antibiotics is also a serious worry. The researchers are currently developing a new class of anti-toxin treatment based on these findings. One advantage of such antitoxins, says Dr. Stamler, is that resistance won’t occur. The researchers hope that the new treatment can enter clinical trials very rapidly.

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Newly Discovered Icelandic Current Could Change North Atlantic Climate Picture

Science Daily  — An international team of researchers, including physical oceanographers from the Woods Hole Oceanographic Institution (WHOI), has confirmed the presence of a deep-reaching ocean circulation system off Iceland that could significantly influence the ocean's response to climate change in previously unforeseen ways.

Crucial to this warm-to-cold oceanographic choreography is the Denmark Strait Overflow Water (DSOW), the largest of the deep, overflow plumes that feed the lower limb of the conveyor belt and return the dense water south through gaps in the Greenland-Scotland Ridge.

The current, called the North Icelandic Jet (NIJ), contributes to a key component of the Atlantic Meridional Overturning Circulation (AMOC), also known as the "great ocean conveyor belt," which is critically important for regulating Earth's climate. As part of the planet's reciprocal relationship between ocean circulation and climate, this conveyor belt transports warm surface water to high latitudes where the water warms the air, then cools, sinks, and returns towards the equator as a deep flow.

For years it has been thought that the primary source of the Denmark Overflow is a current adjacent to Greenland known as the East Greenland Current. However, this view was recently called into question by two oceanographers from Iceland who discovered a deep current flowing southward along the continental slope of Iceland. They named the current the North Icelandic Jet and hypothesized that it formed a significant part of the overflow water.

Now, in a paper published in the Aug. 21 online issue of the journal Nature Geoscience, the team of researchers -- including the two Icelanders who discovered it -- has confirmed that the Icelandic Jet is not only a major contributor to the DSOW but "is the primary source of the densest overflow water."

"In our paper we present the first comprehensive measurements of the NIJ," said Robert S. Pickart of WHOI, one of the authors of the study. "Our data demonstrate that the NIJ indeed carries overflow water into Denmark Strait and is distinct from the East Greenland Current. We show that the NIJ constitutes approximately half of the total overflow transport and nearly all of the densest component.

The researchers used a numerical model to hypothesize where and how the NIJ is formed. "We've identified a new paradigm," he said. "We're hypothesizing a new, overturning loop" of warm water to cold.

The results, Pickart says, have "important ramifications" for ocean circulation's impact on climate. Climate specialists have been concerned that the conveyor belt is slowing down due to a rise in global temperatures. They suggest that increasing amounts of fresh water from melting ice and other warming-related phenomena are making their way into the northern North Atlantic, where it could freeze, which would prevent the water from sinking and decrease the need for the loop to deliver as much warm water as it does now. Eventually, this could lead to a colder climate in the northern hemisphere.

While this scenario is far from certain, it is critical that researchers understand the overturning process, he said, to be able to make accurate predictions about the future of climate and circulation interaction. "If a large fraction of the overflow water comes from the NIJ, then we need to re-think how quickly the warm-to-cold conversion of the AMOC occurs, as well as how this process might be altered under a warming climate," Pickart said.

"These results implicate local water mass transformation and exchange near Iceland as central contributors to the deep limb of the Atlantic Meridional Overturning Circulation, and raise new questions about how global ocean circulation will respond to future climate change," said Eric Itsweire, program director in the U.S. National Science Foundation (NSF)'s Division of Ocean Sciences, which funded the research.

The Research Council of Norway also funded the analysis of the data.

Pickart and a team of scientists from the U.S., Iceland, Norway, and the Netherlands are scheduled to embark on Aug. 22 on a cruise aboard the WHOI-operated R/V Knorr to collect new information on the overturning in the Iceland Sea.

"During our upcoming cruise on the Knorr we will, for the first time, deploy an array of year-long moorings across the entire Denmark Strait to quantify the NIJ and distinguish it from the East Greenland Current," Pickart said. "Then we will collect shipboard measurements in the Iceland Sea to the north of the mooring line to determine more precisely where and how the NIJ originates."

In addition to Pickart, authors of the Nature Geoscience study include Michael A. Spall, and Daniel J. Torres of WHOI, lead author Kjetil Våge, a graduate of the MIT-WHOI joint program now with University of Bergen, Norway, Svein Østerhus and Tor Eldevik, also of the University of Bergen, Norway, and Héðinn Valdimarsson and Steingrímur Jónsson -- the two discoverers of the NIJ -- of the Marine Research Institute in Reykjavik, Iceland.