Nestin, an intermediate filament protein widely used as a marker of neural progenitors, was recently found to be expressed transiently in developing cortical neurons in culture and in developing mouse cortex. In young cortical cultures, nestin regulates axonal growth cone morphology. In addition, nestin, which is known to bind the neuronal cdk5/p35 kinase, affects responses to axon guidance cues upstream of cdk5, specifically, to Sema3a. Changes in growth cone morphology require rearrangements of cytoskeletal networks, and changes in microtubules and actin filaments are well studied. In contrast, the roles of intermediate filament proteins in this process are poorly understood, even in cultured neurons. Here, we investigate the molecular mechanism by which nestin affects growth cone morphology and Sema3a sensitivity. We find that nestin selectively facilitates the phosphorylation of the lissencephaly-linked protein doublecortin (DCX) by cdk5/p35, but the phosphorylation of other cdk5 substrates is not affected by nestin. We uncover that this substrate selectivity is based on the ability of nestin to interact with DCX, but not with other cdk5 substrates. Nestin thus creates a selective scaffold for DCX with activated cdk5/p35. Last, we use cortical cultures derived from Dcx KO mice to show that the effects of nestin on growth cone morphology and on Sema3a sensitivity are DCX-dependent, thus suggesting a functional role for the DCX-nestin complex in neurons. We propose that nestin changes growth cone behavior by regulating the intracellular kinase signaling environment in developing neurons. The sex of animal subjects is unknown.

SIGNIFICANCE STATEMENT Nestin, an intermediate filament protein highly expressed in neural progenitors, was recently identified in developing neurons where it regulates growth cone morphology and responsiveness to the guidance cue Sema3a. Changes in growth cone morphology require rearrangements of cytoskeletal networks, but the roles of intermediate filaments in this process are poorly understood. We now report that nestin selectively facilitates phosphorylation of the lissencephaly-linked doublecortin (DCX) by cdk5/p35, but the phosphorylation of other cdk5 substrates is not affected. This substrate selectivity is based on preferential scaffolding of DCX, cdk5, and p35 by nestin. Additionally, we demonstrate a functional role for the DCX-nestin complex in neurons. We propose that nestin changes growth cone behavior by regulating intracellular kinase signaling in developing neurons.

Calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, are widely used as standard immunosuppressants in organ transplantation recipients. However, these drugs can cause severe pain in patients, commonly referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Although calcineurin inhibition increases NMDAR activity in the spinal cord, the underlying mechanism remains enigmatic. Using an animal model of CIPS, we found that systemic administration of FK506 in male and female mice significantly increased the amount of α2-1–GluN1 complexes in the spinal cord and the level of α2-1–bound GluN1 proteins in spinal synaptosomes. Treatment with FK506 significantly increased the frequency of mEPSCs and the amplitudes of monosynaptic EPSCs evoked from the dorsal root and puff NMDAR currents in spinal dorsal horn neurons. Inhibiting α2-1 with gabapentin or disrupting the α2-1–NMDAR interaction with α2-1Tat peptide completely reversed the effects of FK506. In α2-1 gene KO mice, treatment with FK506 failed to increase the frequency of NMDAR-mediated mEPSCs and the amplitudes of evoked EPSCs and puff NMDAR currents in spinal dorsal horn neurons. Furthermore, systemic administration of gabapentin or intrathecal injection of α2-1Tat peptide reversed thermal and mechanical hypersensitivity in FK506-treated mice. In addition, genetically deleting GluN1 in dorsal root ganglion neurons or α2-1 genetic KO similarly attenuated FK506-induced thermal and mechanical hypersensitivity. Together, our findings indicate that α2-1–bound NMDARs mediate calcineurin inhibitor-induced tonic activation of presynaptic and postsynaptic NMDARs at the spinal cord level and that presynaptic NMDARs play a prominent role in the development of CIPS.

SIGNIFICANCE STATEMENT Calcineurin inhibitors are immunosuppressants used to prevent rejection of transplanted organs and tissues. However, these drugs can cause severe, unexplained pain. We showed that calcineurin inhibition enhances physical interaction between α2-1 and NMDARs and their synaptic trafficking in the spinal cord. α2-1 is essential for calcineurin inhibitor-induced aberrant activation of presynaptic and postsynaptic NMDARs in the spinal cord. Furthermore, inhibiting α2-1 or disrupting α2-1–NMDAR interaction reduces calcineurin inhibitor-induced pain hypersensitivity. Eliminating NMDARs in primary sensory neurons or α2-1 KO also attenuates calcineurin inhibitor-induced pain hypersensitivity. This new information extends our mechanistic understanding of the role of endogenous calcineurin in regulating synaptic plasticity and nociceptive transmission and suggests new strategies for treating this painful condition.

Persistent alterations in neuronal activity elicit homeostatic plastic changes in synaptic transmission and/or intrinsic excitability. However, it is unknown whether these homeostatic processes operate in concert or at different temporal scales to maintain network activity around a set-point value. Here we show that chronic neuronal hyperactivity, induced by M-channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in cultured hippocampal pyramidal neurons from mice of either sex. Homeostatic changes of intrinsic excitability occurred at a fast timescale (1–4 h) and depended on ongoing spiking activity. This fast intrinsic adaptation included plastic changes in the threshold current and a distal relocation of FGF14, a protein physically bridging Na_v1.6 and K_v7.2 channels along the axon initial segment. In contrast, synaptic adaptations occurred at a slower timescale (~2 d) and involved decreases in miniature EPSC amplitude. To examine how these temporally distinct homeostatic responses influenced hippocampal network activity, we quantified the rate of spontaneous spiking measured by multielectrode arrays at extended timescales. M-Channel blockade triggered slow homeostatic renormalization of the mean firing rate (MFR), concomitantly accompanied by a slow synaptic adaptation. Thus, the fast intrinsic adaptation of excitatory neurons is not sufficient to account for the homeostatic normalization of the MFR. In striking contrast, homeostatic adaptations of intrinsic excitability and spontaneous MFR failed in hippocampal GABAergic inhibitory neurons, which remained hyperexcitable following chronic M-channel blockage. Our results indicate that a single perturbation such as M-channel inhibition triggers multiple homeostatic mechanisms that operate at different timescales to maintain network mean firing rate.

SIGNIFICANCE STATEMENT Persistent alterations in synaptic input elicit homeostatic plastic changes in neuronal activity. Here we show that chronic neuronal hyperexcitability, induced by M-type potassium channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in hippocampal excitatory neurons. The data indicate that the fast adaptation of intrinsic excitability depends on ongoing spiking activity but is not sufficient to provide homeostasis of the mean firing rate. Our results show that a single perturbation such as M-channel inhibition can trigger multiple homeostatic processes that operate at different timescales to maintain network mean firing rate.

Wednesday 5 June marks World Environment Day and an opportunity for everyone to take action on the critical issue of food waste and losses. “Think. Eat. Save” is the theme, echoing the name of the campaign launched recently by FAO and UNEP, which encourages people to reduce their “foodprint” by making more informed choices. Every year 1.3 billion tonnes of food [...]

FAO has begun field tests for a new approach to measuring hunger and food insecurity – part of a collaboration with polling specialists Gallup, Inc. The project – known as Voices of the Hungry – is based on a “food insecurity experience scale,” with annual data collected using eight interview questions about people’s experiences of food insecurity over the preceding [...]

FAO and its partners have launched an initiative aimed at cutting food waste across the Asia-Pacific region. Save Food Asia-Pacific Campaign targets losses both straight after harvest and between the market and people’s plates. FAO estimates that reducing global food waste by just one quarter would be sufficient to feed the 870 million people suffering from chronic hunger in the world. [...]

FAO Director-General José Graziano da Silva underlined his firm belief that a hunger-free world is possible "within our lifetimes," during high-level talks in New York. "The Zero Hunger Challenge calls for something new – something bold, but long overdue," he said. It was a "decisive global commitment to end hunger, eliminate childhood stunting, make all food systems sustainable, eradicate rural poverty, [...]

FAO will use World Food Day this year to promote one of the five pillars of Zero Hunger Challenge. The theme of the campaign will be “Sustainable Food Systems for Food Security and Nutrition.” Events in more than 120 countries – supported by videos, an issues paper, posters, media interviews and more – will communicate the message that our food systems [...]

We will only achieve zero hunger if we speak on behalf of those unable to represent themselves. That was a key message during an event titled “Zero Hunger: are we ready?” at FAO headquarters in Rome, Italy, on Friday, 11 October. “Hungry people have no voice, they are different from all others,” said FAO Director-General José Graziano da Silva (pictured, left). “We [...]

Help raise the profile of the IYFF 2014 and its role in eradicating hunger Family farming is the predominant form of agriculture in the world with more than 500 million family farmers playing a key role in securing a future where more quality food is produced in a sustainable way.  For this reason, the 2014 International Year of Family Farming plays a [...]

FAO is working to help typhoon-affected farmers to ensure the next harvests in 2014 – You can help as well. Philippine farmers need urgent assistance  to avoid a double tragedy befalling rural survivors of Typhoon Haiyan. The typhoon hit just as farmers were beginning a new planting season, and FAO estimates that over one million farmers have been affected and hundreds of [...]

Total food losses have been estimated at 1.3 billion tons per year, which represents roughly one-third of the world food production for human consumption. The economic value of food losses and waste amounts to $680 billion in industrialized countries and $310 billion in developing countries. In total, food loss and waste amount to one trillion dollars globally. Lost and wasted food [...]

Once known as “the gold of the Incas,” quinoa has been one of the world’s neglected crops but is currently becoming more and more popular. For centuries, quinoa remained a hidden treasure grown almost exclusively by indigenous communities in the Andean heights. Lately, quinoa has been growing in popularity with foodies and health-conscious consumers around the world. It was even [...]

Did you know that cash transfer (CT) programmes in countries of the sub-Saharan Africa actually have a significant impact? In Malawi, these programmes helped families invest in agricultural equipment and livestock to produce their own food and reduce levels of negative coping strategies, like begging and school drop-outs. In Kenya, secondary school attendance rose by 9 percent and access to [...]

Enjoy a low-cost, healthy diet from your very own vegetable garden and get the chance to make money by selling your own products. Start your own vegetable garden to grow, prepare and eat your own delicious fruits and vegetables with these tips: Do your research: When you begin your own vegetable garden you should understand the type of soil you work [...]

Have you ever wondered if you are getting adequate nutrients from the food you eat? It is a common misconception that malnutrition means not getting enough food. This is, however, incorrect! People who take in insufficient food can be malnourished, but also those who consume too much face the same risks. Malnutrition is defined as “An abnormal physiological condition caused by [...]

Forests and trees sustain and protect us, providing clean air and water, safeguarding biodiversity and acting as a buffer against climate change. For many people, they also offer food, shelter and employment. Here are ten facts about trees you might not be aware of: The  world’s forests store 289 gigatonnes (Gt) of carbon in their biomass alone. Deforestation accounts for up to 20% [...]

International Kungfu superstar and renowned Hollywood film actor Jackie Chan has joined FAO in the fight against hunger. In a recent visit to Ethiopia, Chan met with beneficiaries of the ‘Purchase from Africans for Africa’ (PAA) project as well as a South-South Cooperation Programme where he discussed with Chinese experts how they exchange technical knowledge with Ethiopian farmers to help them [...]

Today leading international experts on climate change, the IPCC, presented their latest report on the impacts of climate change on humanity, and what we can do about it. It’s a lengthy report, so we’ve shrunk it down to Oxfam's five key takeaways on climate change and hunger. 1. Climate change: the impacts on crops are worse than we thought Climate change has [...]

As FAO launches dedicated webpages on post-2015, here are seven things to know about the process and how FAO is playing its part. 7 - Post-2015 development agenda - The name refers to the process through which Member States agree on a new global development framework to succeed the Millennium Development Goals (MDGs), eight goals that followed the UN Millennium Declaration [...]

The mission for an end to hunger in the world’s most populous region has received a boost, with member countries responding positively to a call by FAO for a “massive effort” to end hunger in Asia and the Pacific. 1. Asia-Pacific is home to nearly two-thirds of the world’s chronically hungry people. |True|     Asia-Pacific, with over 4.2 billion people, is home [...]

‘‘—the first 1000 days are a critical window in a child’s development, but let’s not forget this child on day 1,001.’’ School nutrition programmes help to address the +1,001 day gap. Today, perceptions of school gardens are changing in response to increasingly urgent needs for greater food security, environmental protection, more secure livelihoods and better nutrition. School gardens have new multiple [...]

People have never consumed so much fish or depended so greatly on the sector for their well-being as they do today. Did you know?  Fish is one of the most-traded food commodities worldwide, worth almost US$130 billion in 2012 – a figure that will probably continue to increase. World per capita apparent fish consumption increased from an average of 9.9 kg in the [...]

The challenge is to maintain and develop the socioeconomic benefits from forests while safeguarding the resource. FAO’s State of the World’s Forests (SOFO) 2014 argues that if the focus of data collection and policy is shifted from trees to people, forests can be sustainably managed to meet society’s growing demands. Read the most important findings: The formal forestry sector employs some 13.2 [...]

Today’s fisheries sector hosts a multibillion dollar industry that is a vital source of food and nutrition, employment, trade, economic wellbeing and recreation. What is blue growth? The concept of a "blue economy" came out of the 2012 Rio+20 Conference and emphasizes conservation and sustainable management, based on the premise that healthy ocean ecosystems are more productive and a must for sustainable [...]

Malnutrition isn’t just a problem of hunger in developing countries—it exists in all regions and across socio-economic classes. The effects on human health Besides undernutrition, malnutrition also includes micronutrient-deficient diets and overweight and obesity. Chronic malnutrition can have serious, often life-threatening, health consequences, especially for children. Undernutrition can lead to physical and cognitive stunting, and makes children more susceptible to infectious diseases. Micronutrient deficiencies [...]

Hundreds of millions of people around the world continue to suffer from hunger and malnutrition. Governments are urged to make stronger commitments at November’s Second International Conference on Nutrition (ICN2) to ensure healthier diets for all. That's according to the Food and Agriculture Organization and the World Health Organization of the United Nations. Watch this video to find out the challenges that [...]

Farmer field schools (FFS) are essentially schools without walls that introduce new technological innovations while building on indigenous knowledge. In FFS, farmers are the experts. Key features and principles of the FFS approach – TRUE or FALSE? The FFS approach allows farmers to learn through testing changes in a controlled, group-based environment TRUE:  Discovery-based learning is an essential part of the FFS as [...]

Each year, 30 percent of global food production is lost after harvest or wasted in shops, households and catering services. This represents 750 billion USD in terms of producer or farmgate prices, going up to almost a trillion US dollars of trade value of food every year – half the GDP of Italy!If nature asked us to pay the total [...]

Biodiversity for food and agriculture is among the earth’s most important resources. Biodiversity is indispensable: be it the insects that pollinate plants, the microscopic bacteria used for making cheese, the diverse livestock breeds used to make a living in harsh environments, the thousands species of fish, and other aquatic species in our lakes, rivers and oceans, or the thousands of [...]

In its simplest form, a kitchen garden produces fresh fruits, vegetables and herbs for delicious, healthy meals. Research suggests that kitchen gardens can supply up to half of all non-staple food needs, as well as a significant number of vitamins and minerals. This makes them an invaluable tool for food security in vulnerable communities. ‘Imagine one day you lost everything you owned.  [...]

Forests are one of the Earth’s greatest natural resources. There is a reason why we often figuratively speak of ‘the tree of life’; forests are key to supporting life on Earth. Eight thousand years ago, half of the Earth’s land surface was covered by forests or wooded areas. Today, these areas represent less than one third. Forests are home to 80% [...]

The United Nations launched the 2014 International Year of Family Farming to stress the vast potential family farmers have to eradicate hunger and preserve natural resources. In both developed and developing countries, more than 500 million, or nine out of ten, farms are managed by families, making family farms the predominant form of agriculture. They not only produce about 80% [...]

Join us virtually on the Dr Fridtjof Nansen, a marine research vessel, as it embarks on a month-long cruise departing from Cape Town, South Africa, to conduct scientific research in the deep seas of the Southeast Atlantic Fisheries Organization (SEAFO) convention area before arriving at Walvis Bay, Namibia.  Since 1975, FAO and the Norwegian Agency for Development Cooperation have collaborated with [...]

All over the world local varieties of fruit, vegetables and grain are grown. Many are seemingly forgotten or are underutilized despite having outstanding nutritional or taste qualities. Some have good commercial potential and could be an excellent cash crop for a smallscale or family farmers, aimed at the local, regional or international market. Here are six traditional crops and six facts [...]

They are delicious, they are nutritious and they make your mouth water.  If you know your apples from your oranges, then pit your wits against our fruit quiz. You will need to guess where different fruits come from, where they are most popular and how good they are for you. Let’s get started. 1. Which country is the biggest producer of dates? A.    [...]

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It’s been around for thousands of years; the UN General Assembly named an international year for it in 2013; and now it has been sent into space. Quinoa is a superfood in more ways than one. It is a good source of protein, the highest of all the whole grains; and its edible seeds provide all of the essential amino acids the body [...]

We took a look around and put together a list of  Twitter accounts to keep you informed about what is happening in the world of soils.  Here are, in alphabetical order, ten voices on twitter you should follow for the latest on soils: @agriculturesnet The AgriCultures Network shares knowledge on small-scale family farming and agroecology. With agroecology we can build soils for life! http://t.co/pN62odtLt9 [...]

Whether we categorize uneaten food as “lost” or “wasted” depends on where it goes out of the food supply chain. Imagine how everything we eat travels across a food supply chain, a complex journey that stretches from farm to table. Studies show that an astounding 1/3 of all the food we produce for human consumption never actually reaches our plates. Most [...]

As part of a balanced diet, milk and dairy products can be an important source of dietary energy, protein and fat. But, the scientific evidence is massing up that regular consumption of large quantities of milk can be bad for your health, and campaigners are making noise about the environmental and international costs of large-scale intensive dairy farming. We put together [...]

“Children subjected to child labour need our support and action so they can enjoy their right to education and health and become productive farmers and workers as adults to escape poverty and hunger.” - José Graziano da Silva, FAO Director- General  Child labour is not unique to a particular country, ethnicity, culture, or ideology. Today, there are about 100 million boys [...]

What happens when money is given directly to people living in dire conditions? Will children be better nourished? Will families be more productive or will they become dependent? Will economies grow stronger? Today, some 70 percent of the world population, most of which live in rural areas, have no access to adequate social protection measures. For this reason, FAO has [...]

Feeding the world’s growing population, which is expected to go beyond 9 billion by 2050, is one of the world’s biggest challenges. Some of the highest rates of population growth are predicted to occur in areas that are highly dependent on the agriculture sector (i.e. crops, livestock, forests and fisheries). Sustainable agricultural growth is one of the most effective means [...]

From a media bed unit start-up in Bangkok to a fully developed 120 households deep water culture (DWC) unit in Ethiopia, aquaponics is showcasing its true potential to produce sustainable food anytime, anywhere. A marriage between aquaculture (raising aquatic animals such as fish, snails or prawns in tanks) and hydroponics (cultivating plants in water), aquaponics is a ‘clean and green’ [...]

The photos below were entries in the XIV World Forestry Congress ‘Forests and People’ photo contest. Take a tour with us around the world and learn interesting facts on forests and the socioeconomic benefits they provide to people around the world. 

Bees pollinate a third of what we eat and play a vital role in sustaining the planet’s ecosystems. Some 84% of the crops grown for human consumption need bees or other insects to pollinate them to increase their yields and quality. Bee pollination not only results in a higher number of fruits, berries or seeds, it may also give a [...]

Fish plays an important role in fighting hunger and malnutrition and is the main source of animal protein in many developing countries. Seafood is not only a source of proteins and healthy long-chain omega-3 fats, but also an essential source of other nutrients like iodine, vitamin D and calcium, which are crucial to living a healthy life. Here are 10 interesting [...]

As we celebrate our 70-year anniversary, find out how much you know about the work that FAO is doing around the world. Answer these 7 questions and help us fight hunger by becoming an ambassador of FAO!

Pulses have been consumed for at least 10 000 years and are among the most extensively used foods in the world. They provide protein and fibre, and are a great source of vitamins and minerals, such as iron, zinc and magnesium. You probably already eat more pulses than you realize but can you put your finger on these facts on pulses? [...]