California just made school accountability much more complicated. And that's good.

Democrat Gavin Newsom, who takes office Jan. 7, plans to expand full-day kindergarten and child-care offerings in the state, according to media reports.

Utah is one of four states where state laws conflict with components of the federal Every Student Succeeds Act meaning districts may have to answer to two separate accountability systems this fall.

An activist's lawsuit is an example of how many states, because of outdated software, have trouble answering the public's demand to detail how billions of K-12 dollars are spent.

A new study says that problems surrounding child-care hurt Georgia parents economically in many ways including in turned down promotions and having to cut back on work and school hours.

Florida's governor signed a bill that will allow schools to arm classroom teachers, part of a longer list of school safety changes made after a school shooting in Parkland, Fla., last year.

A bill prohibiting anti-Semitism in Florida's public schools and universities is going to Republican Gov. Ron DeSantis.

Performance assessments have the potential to ensure that instruction for students with disabilities is aligned with state standards.

Alexandria Area High School was created to accommodate changes in education and technology.

When can we expect the Islanders to get healthy?

The U.S. Supreme Court took up the question of whether courts must find a juvenile offender permanently incorrigible before a sentence of life without parole.

But some Democrats say that could make the selection process more political.

Michele Deodato
Oct 2, 2024; 44:e2308232024-e2308232024
BehavioralSystemsCognitive

Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular

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.

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca²⁺-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca²⁺ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca²⁺ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca²⁺-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

Large-scale genome-wide association studies (GWASs) have associated intronic variants in PDE4B, encoding cAMP-specific phosphodiesterase-4B (PDE4B), with increased risk for post-traumatic stress disorder (PTSD), as well as schizophrenia and substance use disorders that are often comorbid with it. However, the pathophysiological mechanisms of genetic risk involving PDE4B are poorly understood. To examine the effects of PDE4B variation on phenotypes with translational relevance to psychiatric disorders, we focused on PDE4B missense variant M220T, which is present in the human genome as rare coding variant rs775201287. When expressed in HEK-293 cells, PDE4B1-M220T exhibited an attenuated response to a forskolin-elicited increase in the intracellular cAMP concentration. In behavioral tests, homozygous Pde4b^M220T male mice with a C57BL/6JJcl background exhibited increased reactivity to novel environments, startle hyperreactivity, prepulse inhibition deficits, altered cued fear conditioning, and enhanced spatial memory, accompanied by an increase in cAMP signaling pathway-regulated expression of BDNF in the hippocampus. In response to a traumatic event (10 tone–shock pairings), neuronal activity was decreased in the cortex but enhanced in the amygdala and hippocampus of Pde4b^M220T mice. At 24 h post-trauma, Pde4b^M220T mice exhibited increased startle hyperreactivity and decreased plasma corticosterone levels, similar to phenotypes exhibited by PTSD patients. Trauma-exposed Pde4b^M220T mice also exhibited a slower decay in freezing at 15 and 30 d post-trauma, demonstrating enhanced persistence of traumatic memories, similar to that exhibited by PTSD patients. These findings provide substantive mouse model evidence linking PDE4B variation to PTSD-relevant phenotypes and thus highlight how genetic variation of PDE4B may contribute to PTSD risk.

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by -secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V₃₂₁L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V₃₂₁L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V₃₂₁L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V₃₂₁L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V₃₂₁L mouse and humans with SCZ.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (I_h), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca²⁺-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, I_h, and death, compromising audition at the young adult stage in HCN1^+/+, but not in HCN1^–/– genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca²⁺ overload, neuronal death, and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.

Resource Mobilization (RM) has replaced the term fundraising as it expanded to account for not only funds but also human resources, goods and services. It is a fundamental component of [...]

Rome - The Food and Agriculture Organization of the United Nations (FAO) and Grow Asia, a multi-stakeholder partnership platform that brings together farmers, the private sector, governments, [...]

Read the series on how FAO increased efficiency, effectiveness and transparency to better support its Members in the transformation of agrifood systems.

The "Manned Orbiting Laboratory," or "MOL," was built to capture high-resolution images of Soviet targets on the ground. It was so advanced, it could pick up objects on earth as small as a baseball

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.

After Hurricane Ike destroyed thousands of homes and inflicted an estimated $30 billion in damages in 2008, engineers hatched an ambitious plan to protect southeast Texas and its coastal refineries and shipping routes from violent storms. The $34 billion collaboration spearheaded by the U.S. Army Corps of Engineers is a harbinger of the type of massive public works projects that could be required to protect coastal cities like New York and Miami as sea levels rise and hurricanes become less predictable and more severe due to climate change. Smithsonian magazine contributor and Texas native Xander Peters reflects on his experiences growing up in a hurricane corridor and tells us how the wildly ambitious effort came together. Then, Eric Sanderson, an ecological historian, tells us how the project could be applied to other low-lying coastal cities. Read Xander Peters' Smithsonian magazine story about the Ike Dike here (https://www.smithsonianmag.com/science-nature/galveston-texas-plan-stop-next-big-storm-hurricane-ike-180984487/) . Let us know what you think of our show, and how we can make it better, by completing our There's More to That listener survey here (https://docs.google.com/forms/d/e/1FAIpQLSfS90zjBZ2oGa9JxVa-R5affKcOHaR2-ib1_KZeWm3HDQXJIA/viewform) . Find prior episodes of our show here (https://www.smithsonianmag.com/podcast/) . Listen to the New York Botanical Garden podcast "Plant People" here (https://www.nybg.org/plantpeople/) . 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.

In the spring of 1945, with the Third Reich crumbling, the Nazis hid their stolen art in a sealed salt mine. But when U.S. troops arrived, they found that the opening to the mine had been destroyed.

Smithsonian magazine's poetry consultant recites his poem commissioned for a special photography issue

Scientists have created "a form of information immortality" meant to instruct future species on how to recreate humans. But who, or what, will find it?

The sprawling estate, which is the largest privately owned home in the country, will open its doors in November after a month-long closure

Created in London in the 1960s, the tracks are heading to auction as part of a larger collection of memorabilia connected to the famous American guitarist

Geologists suggest the catastrophic impact of "S2" delivered key nutrients to the oceans, prompting microorganisms to thrive

The union for wildland firefighters says a recently passed Ontario bill that makes them eligible for presumptive cancer care under the Workplace Safety and Insurance Board doesn't go far enough.

Wildland firefighters were at Queen’s Park on Wednesday to outline why they feel a new bill that extends protections for cancers, heart injuries and post-traumatic stress disorder linked to their occupation falls short.

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.

Leading CAD Software Optimizes Core Design Functions for an Improved Design Experience

New Solution Helps Designers Calculate and Reduce the Environmental Impact of Their Materials, Production Methods

DWGgateway plug-in lets AutoCAD users share designs with virtually anyone

Leading assembly automation and testing company to standardize on SolidWorks Office Professional, securely manage design data with PDMWorks

New DWGgateway plug-in allows any version of AutoCAD to read and write any DWG file

Software donation to help fuel engineering enthusiasm for students solving real-world challenges

Test enables teachers, potential employers to evaluate students' modeling skills as well as their grasp of engineering principles

Ireland-based manufacturer custom designs forklifts to fit customers' warehouse space

UK consultancy reduces design cycles by weeks, cuts prototyping costs, and designs better products for global clients like Virgin Mobile and Hasbro