St. Louis led 2-0 after two periods, was outscored 3-0, allowed game-winner to Pastrnak with 1:47 remaining

α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3α^A687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.

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.

Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific synaptic connection. While postsynaptic deletion of Mef2c weakens L4 synaptic inputs, it has no effect on inputs from local L2/3, contralateral S1, or the ipsilateral frontal/motor cortex. Similarly, homozygous or heterozygous deletion of Mef2c in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Postsynaptic MEF2C is specifically required during an early postnatal, experience-dependent, period for L4 to L2/3 synapse function, and expression of transcriptionally active MEF2C (MEF2C-VP16) rescues weak L4 to L2/3 synaptic strength in sensory-deprived mice. Together, these results suggest that experience- and/or activity-dependent transcriptional activation of MEF2C promotes development of L4 to L2/3 synapses. Additionally, MEF2C regulates the expression of many pre- and postsynaptic genes in postnatal cortical neurons. Interestingly, MEF2C was necessary for activity-dependent expression of many presynaptic genes, including those that function in transsynaptic adhesion and neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.

The Liège-Guillemins railway station looks like it belongs far in the future: a vast curving monolith of glass, steel and concrete curves extending high above the train tracks. Just as astonishing as its design is the fact that it was built while the normal train schedules continued, with no disruption.

Eclipses have been a subject of fascination throughout human history, and the fact that we now have a clearer understanding of what they actually are—at least in the celestial mechanics sense—than we did in centuries past has not made them any less exciting. With the North American total solar eclipse (https://www.smithsonianmag.com/science-nature/prepare-for-2024s-solar-eclipse-now-with-these-four-key-steps-180981933/) just days away as we’re releasing this episode, and the next one visible from the contiguous United States not due until 2044, we’ll learn about the eclipses from astronomy obsessive (and Smithsonian science correspondent) Dan Falk and hear from Indigenous astronomer Samantha Doxtator about how the Haudenosaunee people have observed and interpreted these mysterious daylight darkenings of the skies over many centuries. You can read Dan’s Smithsonian story about how ancient civilizations responded to eclipses here (https://www.smithsonianmag.com/science-nature/how-ancient-civilizations-reacted-to-eclipses-180983894/) . Find prior episodes of our show here (https://www.smithsonianmag.com/podcast/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Adriana Rosas Rivera, Genevieve Sponsler, Rye Dorsey, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Fact-checking by Stephanie Abramson. Episode artwork by Emily Lankiewicz. Music by APM Music.

This year marks the 100 year anniversary of Japan's gift of cherry blossoms to Washington, D.C.

From the stars moving across the night sky to clouds moving over snow-capped mountains, photographer John Eklund captures the beauty of the region

Have you ever wondered what a solar eclipse is? Join us as we explore the science behind this awe-inspiring celestial event. --- For more videos from Smithsonian Magazine: https://www.smithsonianmag.com/videos/ Digital Editorial Director: Brian Wolly Supervising Producer & Scriptwriter: Michelle Mehrtens Producer: Nicki Marko Video Editor: Sierra Theobald

A mesmerizing 10,000-shot video captures the dramatic life cycles of several species (Owen Reiser)

New DNA analysis adds to growing research indicating the famous Pacific island did not collapse from overuse of resources before the arrival of Europeans

The baby pygmy hippopotamus in a Thailand zoo has taken the internet by storm, and keepers hope she will help gain momentum for conservation efforts

While the annual shower usually makes for a sleepy showing, it has been known to produce fantastic outbursts in the past

Cenotes in the Yucatán Peninsula are time capsules preserving remnants of Maya culture and fossils of extinct megafauna

Concerns are mounting over the potential environmental impact on fish populations following the destruction of Kamloops' historic Red Bridge, which collapsed into the South Thompson River during a fire.

A box found in a Saskatchewan attic, potentially holding millions of dollars worth of hockey cards, is going back up for auction after the original winning bidder never paid up, according to the auction company.

Two buildings collapsed on Hamilton’s Gore Park early Monday morning after being boarded up for over a decade. The fire department says no one was injured and the city has issued an emergency demolition order.

Thousands of people queued up in the city of Geelong, south of Melbourne in Australia, to catch a glimpse of what's once-in-a-decade occurrence -- the blooming 'corpse flower'.

Samsung Galaxy Z Flip FE is rumoured to launch next year, joining the South Korean technology conglomerate’s flagship foldable smartphone lineup as an affordable alternative to the Z Flip series model for buyers. Despite the rumour mill suggesting that it might cut down on some features in an attempt to be priced affordably, a tipster has revealed that the purported smartphone could be powered by the same Exynos processor as the flagship Galaxy S24 series.

Vivo Y18t was silently launched in India as the latest entrant in the company's Y series. The new Vivo handset arrives in two colourways with an IP54-rated build. The Vivo Y18t sports a dual rear camera unit led by a 50-megapixel primary sensor. It runs on a Unisoc T612 chipset with 4GB RAM and 128GB storage. The budget smartphone carries a 5,000mAh battery with 15W fast charging support.

According to Ayurveda and gut health coach Dimple Jangda, smoothies may do more harm than good, especially for your gut health.

Thousands of people queued up in the city of Geelong, south of Melbourne in Australia, to catch a glimpse of what's once-in-a-decade occurrence -- the blooming 'corpse flower'.

According to the latest rumors, the Samsung Galaxy Z Flip FE could be powered by the Exynos 2400 chipset which is surprising.

The post Samsung Galaxy Z Flip FE chipset of choice could surprise you appeared first on Phandroid.

The ASUS ROG Phone 9 has recently been spotted on Geekbench where it appears to be powered by the new Qualcomm chipset.

The post ASUS ROG Phone 9 spotted on Geekbench with Qualcomm’s latest chipset appeared first on Phandroid.

Not less than 13 persons have reportedly died after a mining site collapsed in Bassa local government area of Plateau State. Chairman of the local government, Joshua Riti, who confirmed ths incident, said it occurred on November 10. He added that seven of the deceased hail from Bassa LGA, NAN reports. “This is an unfortunate […]

The post Mining site collapses in Plateau, kills 13 first appeared on Business Hallmark.

Thousands of Serbians demand prime minister's resignation following deadly roof collapse

German opposition welcome snap-election news after ruling coalition's collapse

At a rally to mark International Youth Day on August 12 in Tanzania’s southern Mbeya region, John Mnyika stood with a determined expression, addressing his supporters. The air was charged with anticipation. Mnyika, the Secretary-General of Tanzania’s opposition party, Chadema, was preparing to speak about the upcoming elections when the chaos erupted. Without warning, heavily […]

Forget videos by gamers or influencers. For a real online thrill, watch the world's biggest flower emerging in a former web designer's greenhouse, says Annalee Newitz

Around 3000 years ago, several empires and kingdoms in the Mediterranean collapsed, with a group of sea-faring warriors implicated as the culprit. But new evidence shows that many of our ideas about this turbulent time need completely rethinking

Analysis of pollen in sediment cores from a large lake in Greece shows that nomadic livestock herders took over the region after the collapse of the Western Roman Empire

Historians have claimed the people of Easter Island overexploited natural resources, causing a population crash, but new evidence suggests they lived sustainably for centuries

Title: Blood Test May One Day Predict Breast Cancer Relapse
Category: Health News
Created: 8/26/2015 12:00:00 AM
Last Editorial Review: 8/27/2015 12:00:00 AM

Title: pseudoephedrine
Category: Medications
Created: 8/9/2022 12:00:00 AM
Last Editorial Review: 8/9/2022 12:00:00 AM

Extract

In cystic fibrosis (CF), Pseudomonas aeruginosa acquisition represents a turning point in disease progression. The presence of chronic P. aeruginosa infection is associated with worsening lung function and increased risk of earlier death, whereas treatment substantially improves lung function and survival [1, 2]. Efforts to diagnose and eradicate early P. aeruginosa provide lasting benefits for children with CF [3, 4]. However, the timing of infection varies considerably between individuals with CF, treatment centres [5, 6], and different birth cohorts of people with the disease [7, 8].

Background

Pseudomonas aeruginosa is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing CFTR (CF transmembrane conductance regulator) variations contribute ~85% of the variation in chronic P. aeruginosa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to P. aeruginosa infection.

It's a slightly quieter week after the mass dump of games that was February and the first week of March. Kelley doesn't want her mom to think she's watching hentai, while Anna Marie insists our reviewers don't hate every game. Josh will one day be free of the epic grip of Cold Steel IV, but not before Chris convinces him if he just lifts a truck, he can find a new orbment.

The post RPG Cast – Episode 577: “Eclipse, I Love You, but GO AWAY” appeared first on RPGamer.

Kelley watches DVDs like a caveman. Josh chews on all the expensive things. Meanwhile, Chris stands by some barrels.

The post RPG Cast – Episode 609: “Throwing Corpses at the Door Till You Let Me In” appeared first on RPGamer.

Stroll on down to Uncle Capcom's garage, girls and boys, because it's time to meddle with a cat's voicebox, ride a combat peacock and meticulously injure a vast, blubbery teddybear. By which I mean, the Monster Hunter Wilds beta is now live on Steam through to 4th November at 2.59am GMT. That's 2.59am sharp. If you're hurrying along at 3am on Monday absolutely desperate to polish the aesthetics of a small enslaved catperson, you can sod off and play Dragon Age: The Veilguard instead.

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Putting aside my natural annoyance at Metal Gear Solid Delta: Snake Eater for almost beating out the Twarhammer series in the headline real estate wars, I am more than a little excited to play. Some days, you simply must feast on a tree frog, and while we still don’t have a solid release date, that day doesn’t feel too far away. Good news for stealth fans, and perhaps gooder news for a dozen strapline writers sweating profusely, soiling themselves in anticipation of using “kept you waiting, huh?”.

Until then, I at least have a steady drip feed of new information to keep me sated, the latest of which is the substantial hint that there'll be some new dialogue in the game, as per the video below. Alongside that, the previously pseudonymous Suzetta Miñet - who was credited with voicing EVA in MGS3 and Peace Walker - has revealed herself to be Jodi Benson, the voice of Ariel in Disney’s The Little Mermaid. Cheers for the spot, Automaton West.

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The documentary features accounts from friends and colleagues, including Rana Daggubatti, Taapsee Pannu, and Nagarjuna Akkineni

Paris, France (SPX) Nov 03, 2024
ESA's Proba-3 mission, designed to create a solar eclipse in space, is leaving Europe to head to its Indian launch site. The mission's two spacecraft, designed to align precisely in orbit so one will block the Sun for the other, have departed from Redwire Space's facilities in Kruibeke, Belgium. The pair will be transported to the Satish Dhawan Space Centre near Chennai, India, to prepare for th

The Consumer Electronics Show is a toy wonderland for hi-tech fanciers.

Public Sector Enterprises Selection Board (PSEB) is seeking qualified candidates for the post of managing director at the Karnataka Antibiotics & Pharmaceuticals Limited (KAPL) in Bengaluru. The candidate will be

NPR's Leila Fadel talks with actor Patrick Dempsey about his efforts to raise money for cancer treatment and prevention.