Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with noncanonical receptors and unidentified coreceptors; however, the effects of which are less understood. Using high-throughput tandem mass tag (TMT) liquid chromatography tandem mass spectrometry (LC-MS/MS)-based proteomics and gene set enrichment analysis (GSEA), we identified both shared and unique intracellular pathways activated by Reelin through its canonical and noncanonical signaling in primary murine neurons of either sex during dendritic growth and arborization. We observed pathway cross talk related to regulation of cytoskeleton, neuron projection development, protein transport, and actin filament-based process. We also found enriched gene sets exclusively by the noncanonical Reelin pathway including protein translation, mRNA metabolic process, and ribonucleoprotein complex biogenesis suggesting Reelin fine-tunes neuronal structure through distinct signaling pathways. A key discovery is the identification of aldolase A, a glycolytic enzyme and actin-binding protein, as a novel effector of Reelin signaling. Reelin induced de novo translation and mobilization of aldolase A from the actin cytoskeleton. We demonstrated that aldolase A is necessary for Reelin-mediated dendrite growth and arborization in primary murine neurons and mouse brain cortical neurons. Interestingly, the function of aldolase A in dendrite development is independent of its known role in glycolysis. Altogether, our findings provide new insights into the Reelin-dependent signaling pathways and effector proteins that are crucial for dendritic development.

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep.

Neural circuits supporting innate behaviors, such as feeding, exploration, and social interaction, intermingle in the lateral hypothalamus (LH). Although previous studies have shown that individual LH neurons change their firing relative to the baseline during one or more behaviors, the firing rate dynamics of LH populations within behavioral episodes and the coordination of behavior-related LH populations remain largely unknown. Here, using unsupervised graph-based clustering of LH neurons firing rate dynamics in freely behaving male mice, we identified distinct populations of cells whose activity corresponds to feeding, specific times during feeding bouts, or other innate behaviors—social interaction and novel object exploration. Feeding-related cells fired together with a higher probability during slow and fast gamma oscillations (30–60 and 60–90 Hz) than during nonrhythmic epochs. In contrast, the cofiring of neurons signaling other behaviors than feeding was overall similar between slow gamma and nonrhythmic epochs but increased during fast gamma oscillations. These results reveal a neural organization of ethological hierarchies in the LH and point to behavior-specific motivational systems, the dysfunction of which may contribute to mental disorders.

Dopamine (DA) and norepinephrine (NE) have been repeatedly implicated in neuropsychiatric vulnerability, in part via their roles in mediating the decision-making processes. Although two neuromodulators share a synthesis pathway and are coactivated under states of arousal, they engage in distinct circuits and modulatory roles. However, the specific role of each neuromodulator in decision-making, in particular the exploration–exploitation tradeoff, remains unclear. Revealing how each neuromodulator contributes to exploration–exploitation tradeoff is important in guiding mechanistic hypotheses emerging from computational psychiatric approaches. To understand the differences and overlaps of the roles of these two catecholamine systems in regulating exploration, a direct comparison using the same dynamic decision-making task is needed. Here, we ran male and female mice in a restless two-armed bandit task, which encourages both exploration and exploitation. We systemically administered a nonselective DA antagonist (flupenthixol), a nonselective DA agonist (apomorphine), a NE beta-receptor antagonist (propranolol), and a NE beta-receptor agonist (isoproterenol) and examined changes in exploration within subjects across sessions. We found a bidirectional modulatory effect of dopamine on exploration. Increasing dopamine activity decreased exploration and decreasing dopamine activity increased exploration. The modulatory effect of beta-noradrenergic receptor activity on exploration was mediated by sex. Reinforcement learning model parameters suggested that dopamine modulation affected exploration via decision noise and norepinephrine modulation affected exploration via sensitivity to outcome. Together, these findings suggested that the mechanisms that govern the exploration–exploitation transition are sensitive to changes in both catecholamine functions and revealed differential roles for NE and DA in mediating exploration.

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.

Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between PV and pyramidal cells (PCs) through whole-cell patch–clamp electrophysiology, optogenetics, immunohistochemical analysis, and behaviors in male and female mice. While inhibitory synapse development is adversely affected by PV-specific expression of EphB2, a strong candidate ASD risk gene, astrocytic ephrin-B1 facilitates PV->PC connectivity through a mechanism involving EphB signaling in PV boutons. In contrast, the loss of astrocytic ephrin-B1 reduces PV->PC connectivity and inhibition, resulting in increased seizure susceptibility and an ASD-like phenotype. Our findings underscore the crucial role of astrocytes in regulating inhibitory circuit development and discover a new role of EphB2 receptors in PV-specific inhibitory synapse development.

Rome, 2 December 2014 – The Ministers of Agriculture of the European Union and of other Mediterranean countries welcomed FAO’s transformational changes implemented in the last two years, and underlined [...]

Part of the Feeding Knowledge platform, an initiative [...]

The 2016-17 Programme of Work and Budget will consolidate the existing actions within the Medium Term Plan and the Strategic Framework, emphasizing areas to reflect recent trends and developments, with [...]

A London blacksmith has perfected a technique known as pattern welding to create elaborately-designed replica Saxon swords and knives. He demonstrates his technique on camera.

Caretakers feed the new baby clouded leopards at the Zoo's research facility in Virginia

Equipped with wings and a propeller, Moulton Taylor Aerocar aerobile was capable of taking off from a stoplight or the runway

Looking at the future of geopolitics, the author reveals the surprising results of his research. Read more at http://www.smithsonianmag.com/specialsections/40th-anniversary/George-Friedman-on-World-War-III.html

Recently digitized footage shows the 5th Div. cemetery dedication on Iwo Jima with band, gun salute and officers speaking. In the final scene, tow Marines kneel over the temporary resting place of 3/13 PFC Ernest T. Langbeen. (U.S. Marine Corps History Division and Moving Image Research Collections, University of South Carolina)

Read more about SONG 1: http://j.mp/GTZ0Ru & http://j.mp/GVlcMx Watch how artist Doug Aitken transforms the outside of the art museum into a panoramic movie screen

From the inventor's New Jersey film studio, the delight of cats doing things on film was discovered early in 1894

A learning simulation, combined with fMRI readings, is able to predict the visualizations seen by a dreamer in real time

Our host, Eric Schulze, explains how science is tackling this puzzling question from space.

In 1896, Thomas Edison set off to a remote Canadian district near the Alaska border, with cameras in tow. He succeeded in capturing fascinating images of the prospectors brought in by the Gold Rush.

David Lynch | Smithsonian Magazine’s 2016 American Ingenuity Award Winner for Education As a filmmaker, Lynch has a reputation for creating dark, surreal movies such as Eraserhead, Blue Velvet and Wild at Heart as well as the TV show “Twin Peaks.” In the education world, he's becoming known for something very different: promoting inner peace. Over the past decade, the David Lynch Foundation has sponsored Transcendental Meditation classes for half a million children in places as far-flung as the Bronx, Detroit, Los Angeles, Congo and the West Bank. The program, called Quiet Time, is now at the center of one of the largest-ever studies of meditation for children—a 6,800-pupil research project conducted by the Crime Lab at the University of Chicago and designed to learn if meditation can help kids in highly stressful environments fare better at home and in school. Read more about Lynch’s work: http://smithmag.co/9sHhtm | #IngenuityAwards And more about the American Ingenuity Awards: http://smithmag.co/77xPqy

Researchers recently identified James Fitzjames, a captain on the ill-fated HMS Erebus that went looking for the Northwest Passage in 1845

The predatory pod hunts off the coast of Chile and is led by a matriarch called Dakota

Victor Ambros and Gary Ruvkun discovered microRNA, tiny molecules that play a crucial role in how cells develop, paving the way for new treatments for diseases

The giant salmon carp was formally identified in 1991, and since then, fewer than 30 individuals had been documented

The new research could change history's understanding of the sprawling trade network that connected Europe and the Middle East to East Asia

A "staggering array" of markings have been hiding in plain sight carved into the walls of Gainsborough Old Hall, a 500-year-old home in Lincolnshire, England

This story and others have come to light during a project to translate and digitize a series of texts about archbishops in York, England

During a release of captive-bred snails in September, researchers discovered wild-born individuals from the Partula tohiveana species—which had been considered extinct in the wild—marking a huge milestone in a global effort to save them

Volunteers will be cutting hair at a salon based inside a Cape Breton food bank. The goal is to provide clients with the same salon experience paying customers would receive.

Creating transgenic mosquitoes allows for mechanistic studies of basic mosquito biology and the development of novel vector control strategies. CRISPR–Cas9 gene editing has revolutionized gene editing, including in mosquitoes. This protocol details part of the gene editing process of Aedes aegypti mosquitoes via CRISPR–Cas9, through testing and validating single-guide RNAs (sgRNAs). Gene editing activity varies depending on the sequence of sgRNAs used, so validation of sgRNA activity should be done before large-scale generation of mutants or transgenics. sgRNA is designed using online tools and synthesized in <1 h. Once mutants or transgenics are generated via embryo microinjection, sgRNA activity is validated by quick genotyping polymerase chain reaction (PCR) and DNA sequencing.

Transposon-mediated transgenesis has revolutionized both basic and applied studies of mosquito vectors of disease. Currently, techniques such as enhancer traps and transposon tagging, which rely on remobilizable insertional mutagenesis, are only possible with transposon-based vector systems. Here, we provide general descriptions of methods and applications of transposon-based mosquito transgenesis. The exact procedures must be adapted to each mosquito species and comparisons of some differences among different mosquito species are outlined. A number of excellent publications showing detailed and specific protocols and methods are featured and referenced.

A new exhibition at the British Library explores the public, private and spiritual lives of such figures as Joan of Arc, Christine de Pizan and Hildegard of Bingen

A jury has found a 20-year-old Moncton man guilty of second-degree murder in the 2022 death of an 18-year-old.

The mayor of the eastern P.E.I. town of Three Rivers says comments on social media have become so 'aggressive' that council has decided to hold Tuesday night’s meeting virtually instead of in-person out of concerns for their own safety.

Medical student Samuel Bonne had read everything he could to prepare for his group's dissection of a cadaver. But after the first cut, he left with lingering questions about what it means to lead a good life and die with dignity.

CBC Winnipeg News host Brittany Greenslade speaks with Canadian gynecologist Dr. Jen Gunter, who is part of a Tuesday panel discussion about health misinformation and how to separate fact from fiction. It's part of Together Against Misinformation Week, a nationwide event that runs until Nov. 17.

After nearly six complete seasons, the Canadian Premier League finds itself at an inflection point. Ahead of Saturday’s championship match, it appears there’s some stability — and, consequently, an opportunity to further establish the league’s place within the rapidly growing soccer landscape.

CME Group, the world's leading derivatives marketplace, today announced its new CBL Australian Carbon Credit Unit (ACCU) futures have launched and are available for trading. A total of five...

CRISPR–Cas9 has revolutionized gene editing for traditional and nontraditional model organisms alike. This tool has opened the door to new mechanistic studies of basic mosquito biology as well as the development of novel vector control strategies based on CRISPR–Cas9, including gene drives that spread genetic elements in the population. Although the promise of the specificity, flexibility, and ease of deployment CRISPR is real, its implementation still requires empirical optimization for each new species of interest, as well as to each genomic target within a given species. Here, we provide an overview of designing and testing single-guide RNAs for the use of CRISPR-based gene editing tools.

Transposon-mediated transgenesis of mosquito vectors of disease pathogens followed the early success of transgenesis in the vinegar fly, Drosophila melanogaster. The P transposable element used in Drosophila does not function canonically in mosquitoes, and repeatable, routine transgenesis in mosquitoes was not accomplished until new transposable elements were discovered and validated. A number of distinct transposons were subsequently identified that mediate the introduction of exogenous DNA in a stable and heritable manner in mosquito species, including members of the genera Aedes, Anopheles, and Culex. The most versatile element, piggyBac, is functional in all of these mosquito genera, as well as in many other insects in diverse orders, and has been used extensively outside the class. Transposon-mediated transgenesis of recessive and dominant marker genes and reporter systems has been used to define functional fragments of gene control sequences, introduce exogenous DNA encoding products beneficial to medical interests, and act as "enhancer traps" to identify endogenous genes with specific expression characteristics.

Eliminates the Cost and Complexity of Maintaining Online Parts Catalogs; Improves Search, Navigation, and Communication for Engineers Seeking 3D Part Models

New Licensing, Support Programs For Certification Accompany Software Upgrades

U.K.

3,200 German vocational students in 30 colleges learn engineering fundamentals and prepare for professional careers with SolidWorks software

SolidWorks 3D mechanical design and COSMOS design analysis software prepare students for careers at global enterprises

COSMOS analysis predicts results to estimated 95 percent accuracy of final-stage testing, validating designs most likely to succeed under real-world conditions

Students cut 20 percent out of initial project development time with SolidWorks 3D modeling and COSMOS design analysis software

Permasteelisa selects 1,200 licenses of SolidWorks 3D modeling software to more quickly satisfy clients' high expectations for beautiful and unparalleled function

Names SolidWorks Corporation's suite of COSMOS design analysis software one of the top innovations of 2004

SolidWorks 2006 x64 Edition and COSMOS 2006 x64 Edition revolutionize handling of very large assemblies