Systemic study of pathogenic pathways and interrelationships underlying genes associated with Alzheimer's disease (AD) facilitates the identification of new targets for effective treatments. Recently available large-scale multiomics datasets provide opportunities to use computational approaches for such studies. Here, we devised a novel disease gene identification (digID) computational framework that consists of a semi-supervised deep learning classifier to predict AD-associated genes and a protein–protein interaction (PPI) network-based analysis to prioritize the importance of these predicted genes in AD. digID predicted 1,529 AD-associated genes and revealed potentially new AD molecular mechanisms and therapeutic targets including GNAI1 and GNB1, two G-protein subunits that regulate cell signaling, and KNG1, an upstream modulator of CDC42 small G-protein signaling and mediator of inflammation and candidate coregulator of amyloid precursor protein (APP). Analysis of mRNA expression validated their dysregulation in AD brains but further revealed the significant spatial patterns in different brain regions as well as among different subregions of the frontal cortex and hippocampi. Super-resolution STochastic Optical Reconstruction Microscopy (STORM) further demonstrated their subcellular colocalization and molecular interactions with APP in a transgenic mouse model of both sexes with AD-like mutations. These studies support the predictions made by digID while highlighting the importance of concurrent biological validation of computationally identified gene clusters as potential new AD therapeutic targets.

Different people listening to the same story may converge upon a largely shared interpretation while still developing idiosyncratic experiences atop that shared foundation. What linguistic properties support this individualized experience of natural language? Here, we investigate how the "concrete–abstract" axis—the extent to which a word is grounded in sensory experience—relates to within- and across-subject variability in the neural representations of language. Leveraging a dataset of human participants of both sexes who each listened to four auditory stories while undergoing functional magnetic resonance imaging, we demonstrate that neural representations of "concreteness" are both reliable across stories and relatively unique to individuals, while neural representations of "abstractness" are variable both within individuals and across the population. Using natural language processing tools, we show that concrete words exhibit similar neural representations despite spanning larger distances within a high-dimensional semantic space, which potentially reflects an underlying representational signature of sensory experience—namely, imageability—shared by concrete words but absent from abstract words. Our findings situate the concrete–abstract axis as a core dimension that supports both shared and individualized representations of natural language.

The precise regulation of Ca²⁺ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca²⁺ signals in cultured hippocampal neurons from both female and male rats. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca²⁺ spikes generated by Kv2.1-organized Ca²⁺ microdomains. Furthermore, glucocorticoids rapidly reduced the cell surface expressions of Kv2.1 and Ca_V1.2 channels in hippocampal neurons. In HEK293 cells transfected with Kv2.1 alone, glucocorticoids significantly reduced the surface expression of Kv2.1 with little effect on K⁺ currents. In HEK293 cells transfected with Ca_V1.2 alone, glucocorticoids inhibited Ca_V1.2 currents but had no effect on the cell surface expression of Ca_V1.2. Notably, in the presence of wild-type Kv2.1, glucocorticoids caused a decrease in the surface expression of Ca_V1.2 channels in HEK293 cells. However, this effect was not observed in the presence of nonclustering Kv2.1S586A mutant channels. Live-cell imaging showed that glucocorticoids rapidly decreased Kv2.1 clusters on the plasma membrane. Correspondingly, Western blot results indicated a significant increase in the cytoplasmic level of Kv2.1, suggesting the endocytosis of Kv2.1 clusters. Glucocorticoids rapidly decreased the intracellular cAMP concentration and the phosphorylation level of PKA in hippocampal neurons. The PKA inhibitor H89 mimicked the effect of glucocorticoids on Kv2.1, while the PKA agonist forskolin abrogated the effect. In conclusion, glucocorticoids rapidly suppress Ca_V1.2-mediated Ca²⁺ signals in hippocampal neurons by promoting the endocytosis of Kv2.1 channel clusters through reducing PKA activity.

The artists known as OSGEMEOS showcase the largest exhibition of their work in the United States at the Hirshhorn Museum and Sculpture Garden

A paleontologist at the Natural History Museum in London chronicles the age of the famous and fascinating massive reptiles

The President of the Republic of Azerbaijan, Ilham Aliyev, met today with FAO Director-General José Graziano da Silva at FAO headquarters in Rome.

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Rome - José Graziano da Silva, the [...]

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In a letter addressed to the Director-General, the Ambassador of Malaysia to FAO, on behalf of the Chair of the Asia Group, has announced the endorsement of the [...]

FAO Director-General José Graziano da Silva today expressed confidence that “significant progress against hunger, food insecurity and malnutrition,” will be achieved in the next four years. He made the [...]

New York- FAO Director-General José Graziano da Silva and the President of the UN Security Council (UNSC), Ambassador Ismael Gaspar Martins, have concurred upon the importance of using FAO’s regular [...]

The Director-General addressed the members of the UN Security Council (UNSC) on Tuesday in what was FAO’s first appearance before the principal UN body on global peace and security affairs.

Organized [...]

The 40th Session of the FAO Conference will begin on Monday, 3 July at 9:00 in the Plenary Hall and will continue through Saturday, 8 July 2017. Approximately 600 [...]

Addressing the plenary meeting in the closing session of the 159^th Session of the Council, the Director-General expressed his appreciation to delegates for their commitment and hard work to [...]

On Friday, 7 December during the 160th session of the Council, a side event on the Africa Solidarity Trust [...]

A valuable tool has been produced for decision makers responsible for integrating the Sustainable Development Goals into national policies and programmes. This publication, Transforming food and agriculture to achieve [...]

FAO member nations to choose head of the UN specialized agency in July during the 43rd session of the FAO Conference

Riders--who will descend in inflatable rafts of four rather than alone--will reach speeds of more than 65 miles per hour

Pastry artist Zilly Rosen renders Presidents Lincoln and Obama in cupcake form at the Smithsonian American Art Museum (Meredith Bragg). Read more at http://www.smithsonianmag.com/history-archaeology/Inauguration-2009.html

In about four billion years from now, the Milky Way and Andromeda galaxies will crash together Visualization: NASA, ESA, and F. Summers, STScI Simulation credit: NASA, ESA, G. Besla, Columbia University, and R. van der Marel, STScI

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Every week, the Floyd Country Store draws musicians and their fans from across southwest Virginia

Credit: David Marshall, University of Bristol

In the jungles of Cambodia, villagers travel along abandoned railway tracks on a norry, a rickety transport of spare lumber with a speedy (and loud) motor attached Video, Photographs and Narration by Russ Juskalian

Scientists are researching how the rodent can become less susceptible to its feline foe.

By late September 1918, in a bid to contain the spread of the flu, the U.S. had made the decision to cancel the draft. It was too little, too late—in October alone, over 200,000 Americans were killed by the disease.

In this time-lapse video, watch how workers built a visitor’s center in South Africa using ancient Roman techniques such as the arched ceiling, or vault

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A slowed-down recording, made as part of a scientific study, shows one dog quickly mimicking another canine's expression during playtime in a park in Palermo. (Video courtesy Elisabetta Palagi)

Five categories (People, Arts, Nature, Travel and Mobile) and a grand prize of $2,000.

Selected by Reza for our special issue, this up-and-coming photographer discusses her work

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Think blockbuster movie and you’ve got an idea of how this story ends

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