MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene–circuit–behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.

SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene–circuit–behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2. However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

FAO’s emergency programme to support farmers affected by severe flooding in northern Benin includes creating resilience among communities in order to avert further threats to their livelihoods and food security. Farming families in northern Benin lost crops, livestock and fishing grounds when the Niger River overran its banks in August, just as many villagers were trying to recover from previous floods [...]

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 [...]

Global food security largely depends on smallholder family farms where in many regions of the world women play a crucial role as both producers and providers of food. Studies show that when women and other rural poor have better access to resources, the benefits are far-reaching. Families are healthier, more children attend school, agricultural productivity improves, incomes increase, and rural communities [...]

In the past 20 years, malnutrition in mothers and children has decreased by almost half. But despite this progress, child undernutrition is still the greatest nutrition-related health burden in the world. One of the biggest problems with child undernutrition is that it continues the cycle of stunting: stunted girls grow up to be stunted mothers, and stunted mothers are much [...]

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 [...]

Ecosystem services make human life possible by, for example, providing nutritious food and clean water, regulating disease and climate, supporting the pollination of crops and soil formation, and providing recreational, cultural and spiritual benefits. In 2014, the value of ecosystem services was estimated at a staggering US$ 125 trillion.  Ecosystem services, provided by biodiversity, are fundamental to food production and [...]

When approaching the small house, Hanen can be seen laughing with her family in the yard. Hanen is a 25-year-old biologist living in Ouled Taleb, Siliana, one of several areas in North West Tunisia that are particularly hard-hit by unemployment, low income and high rates of migration. Hanen comes from a poor rural family, who invested in their children’s education [...]

How the beloved figure has become a lightning rod in a heated environmental debate

During WWII, Nazi forces were preparing to take the coastal city of Tobruk and tighten their grip on North Africa

This is the cheesy content readers crave

New research reveals a Tang Dynasty woman's love for sports—and big-eared, braying equids

The vineyard deploys a daily bird-based battalion to pluck snails and insects off their plants

Closed due to COVID-19, the Museum Hotel Antakya looks forward to welcoming guests with its blend of luxury and history once restrictions are lifted

Scientists discover neurotoxin-producing bacteria living on the skin of rough-skinned newts

The virus tweaks bee behavior to infect new hives and may also spread other hive-killing pathogens and pests

The freedom fighter may have once used the structure to conspire against English forces

The specimen may be the earliest known example of a squid-like creature on the attack

Airing on the aquarium's Twitch channel at 4 p.m. EST today, the two-hour session will focus on the video game's diverse insect population

Gelada Monkey staring into the sunset

Two girls run up the rounded walls of the Heydar Aliyev Center in the heart of Baku.

This was one of the most spine chilling experience that I had in my entire time with wildlife It was a winter noon drive that we got into the woods of central India and soon we reached a particular point in the jungle we got intense langur calls saying the presence of a predator around After thorough checking for the same we found this subadult male tiger staring at us from the beside bushes It was really a spine chilling experience to see directly into a tigers eye at any time

A close-up macro depiction of an insect called Eyes Robberfly

The proboscis monkey is a species endemic to Borneo. I areas where they occur they are quite easy to encounter as they have reddish fur and make strange burping sounds for communication.

Monuments in winter

This photo was taken from the Tunnel View at Yosemite National Park. The photo is of Bridalveil Fall consumed by smoke due to controlled burning on the Yosemite Valley floor.

Magenta skies over Monument Valley at sunset.

In 1919, a second wave of cases of the previous year's flu lead to the sudden death of the hockey championship

From virtual museum tours to space exploration, ancient worlds and natural phenomena, this hub has you covered

In 1799, Alexander von Humboldt set foot in the jungles of Cumana, in present-day Venezuela. What ensued was a detailed scientific mission to learn more about the natural world.

Veteran musher Lance Mackey has had his 21st place finish in this year's Iditarod Trail Sled Dog Race vacated because of a failed drug test, race officials announced Thursday.

Now that the New Brunswick COVID-19 curve is flat, risk lies at the borders. What’s considered essential and non-essential travel, and how is New Brunswick making sure people coming in are following safety rules?

The tourism and hospitality industries, which play a large role in the economy of almost every community in northwestern Ontario, are taking a beating during the COVID-19 pandemic. Now, the manager of Tourism Thunder Bay is figuring out how “dire” the situation is, and what could be done to help.

Noy shares her journey of experiencing God's love for herself and forgiving the community that persecuted her family.

God uses Janet to reach people through one-on-one encounters at a bookshop in a closed country.

When Elizabeth May, parliamentary leader of the federal Green Party, proclaimed on Tuesday that "oil is dead," she was correct in a philosophical sense. But not in a practical, real world sense.

A prototype deployed in San Francisco Bay imagines the underside of a floating building as an upside-down artificial reef

Holland America and Princess cruise lines issued notices this week cancelling the remainder of the season in Atlantic Canada, citing global health concerns, and that's taking a huge bite out of the Port of Sydney's budget.

Here’s some culinary inspiration as you wait out a global pandemic

The Metuchen Farmers Market, like many others, has moved to online orders and drive-thru pickups during the coronavirus pandemic