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TRIM46 Is Required for Microtubule Fasciculation In Vivo But Not Axon Specification or Axon Initial Segment Formation

Vertebrate nervous systems use the axon initial segment (AIS) to initiate action potentials and maintain neuronal polarity. The microtubule-associated protein tripartite motif containing 46 (TRIM46) was reported to regulate axon specification, AIS assembly, and neuronal polarity through the bundling, or fasciculation, of microtubules in the proximal axon. However, these claims are based on TRIM46 knockdown in cultured neurons. To investigate TRIM46 function in vivo, we examined male and female TRIM46 knock-out mice. Contrary to previous reports, we find that TRIM46 is dispensable for axon specification and AIS formation. TRIM46 knock-out mice are viable, have normal behavior, and have normal brain structure. Thus, TRIM46 is not required for AIS formation, axon specification, or nervous system function. However, we confirm that TRIM46 is required for microtubule fasciculation. We also show TRIM46 enrichment in the first ~100 μm of axon occurs independently of ankyrinG (AnkG) in vivo, although AnkG is required to restrict TRIM46 only to the AIS. Our results highlight the need for further investigation of the mechanisms by which the AIS and microtubules interact to shape neuronal structure and function.




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Pre- and Postsynaptic MEF2C Promotes Experience-Dependent, Input-Specific Development of Cortical Layer 4 to Layer 2/3 Excitatory Synapses and Regulates Activity-Dependent Expression of Synaptic Cell Adhesion Molecules

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.




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Ask Smithsonian: Does the Five-Second Rule Really Work?

You might think twice about picking that chip off the carpet and putting it into your mouth.




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3D Imaging of the Apollo 11 Capsule - Outside




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Saving a Nest of Baby Rabbits Mauled by a Dog

After a dog digs up a rabbit's nest and leaves a litter exposed, the team at the Toronto Wildlife Center must rehabilitate the malnourished babies before they can be released back into the wild.




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3D Imaging of the Apollo 11 Capsule - Inside




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Historic New Shepard Rocket Booster and Crew Capsule Will Go on Display at the Air and Space Museum

The two artifacts donated by Blue Origin achieved record-breaking feats and will extend the museum's story of trailblazing space travel into the present




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Two High Schoolers Found an 'Impossible' Proof for a 2,000-Year-Old Math Rule—Then, They Discovered Nine More

Ne’Kiya Jackson and Calcea Johnson of Louisiana published a new study proving the Pythagorean theorem using trigonometry, a feat mathematicians long thought could not be done




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Figure skating Grand Prix Final cancelled over travel rules

The figure skating Grand Prix Final next week has been cancelled because of the coronavirus pandemic for the second season in a row. The Dec. 9-12 event in Osaka, Japan, was the only global event matching the best skaters across all four disciplines before the Winter Olympics in Beijing in February.



  • Sports/Olympics/Winter Sports/Figure Skating

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Long list of rules pits Mississauga neighbours against townhouse board

A Mississauga couple is in the midst of a war of words with their townhouse complex's board of directors — which a handful of residents say is imposing unnecessarily strict new rules on the complex's roughly 140 homeowners.



  • News/Canada/Toronto

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Amendments to the Listing Schedule, Delisting of Previously-Listed Contract Months and Subsequent Permanent Delisting of the U.S. Midwest #1 Busheling Ferrous Scrap (AMM) Futures Contract




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Amendments to the Floating Price Rule of the Cobalt Hydroxide CIF China (Fastmarkets) Futures Contract Commencing with the January 2026 Contract Month and Beyond




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Amendments to Rule 867102.E. (“Termination of Trading”) of the HMS 80/20 Ferrous Scrap, CFR Turkey (Platts TSI) Futures Contract.




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Expansion of the Listing Schedule of the Adjusted Interest Rate S&P 500 Total Return Index (EFFR) Futures Contract




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Expansion of the Listing Schedule of the New Crop Weekly Corn and New Crop Weekly Soybean Option Contracts




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SolidWorks Helps Thule Tackle Sports Gear Transport Challenges

Virtual Prototyping Reduces Time and Cost of Physical Tests




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Product Modification Summary: Amendments to the Listing Schedule, Delisting of Previously-Listed Contract Months and Subsequent Permanent Delisting of the U.S. Midwest #1 Busheling Ferrous Scrap (AMM) Futures Contract - Effective November 11, 2024




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Product Modification Summary: Expansion of the Listing Schedule for Certain Commodity Index Futures, Options, and Swaps Contracts - Effective November 18, 2024




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Product Modification Summary: Expansion of the Listing Schedule of the Options on Lean Hog Futures Contract - Effective November 25, 2024




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Product modification Summary: Expansion of the Listing Schedule of the Adjusted Interest Rate S&P 500 Total Return Index (EFFR) Futures Contract - Effective December 9, 2024




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Product Modification Summary: Expansion of the Listing Schedule of the New Crop Weekly Corn and New Crop Weekly Soybean Option Contracts - Effective December 16, 2024




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Schedule for Fall 2024 Evening Series announced

Penn State Mont Alto announces the Fall 2024 schedule for its popular Evening Series of Planetarium Shows, Evening Talks and Star Parties.




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Special Education Bias Rule Put on Hold for Two Years by DeVos Team

As expected, the Education Department has delayed a rule that would require states to take a standardized approach in evaluating districts for minority bias in special education.




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Title IX Rule Details How K-12 Schools Must Address Sexual Harassment, Assault

The Education Department outlines when and how schools must respond to reports of sexual assault and harassment under the Trump administration's interpretation of Title IX, the federal law that prohibits sex discrimination.




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Coaches Immune From Student's Privacy Lawsuit, Appeals Court Rules

Two high school softball coaches are immune from a student's privacy lawsuit because there was no clearly established law barring school officials from discussing a student's private matters with the student's parent.




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District's Hair-Length Rule for Male Basketball Players Struck Down by Court

A federal appeals court has struck down an Indiana school district's policy requiring short hair for boys on the basketball team, ruling that the lack of a similar policy for girls'-team basketball players results in illegal sex discrimination.




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News24 Business | Kenya court rules Meta can be sued over layoffs by contractor

A Kenyan court ruled on Friday that Facebook's parent company Meta could be sued in the East African nation over the dismissal of dozens of content moderators by a contractor.




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Penn State Fayette announces 2024-25 men's, women's home basketball schedules

Penn State Fayette, The Eberly Campus will host 24 basketball games inside its Community Center Main Arena between Nov. 5, 2024, and Feb. 11, 2025.




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New module to support caregivers of children who are neurodivergent

The Clearinghouse for Military Family Readiness at Penn State, in partnership with the Department of Defense, has launched a new parent-education module designed to help parents and caregivers navigate the journey with their children who are neurodivergent or who have autism spectrum disorder.




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Nursing job fair scheduled for Oct. 14 at Penn State Scranton

Penn State Scranton is set to host a job fair for students in its nursing degree program from noon to 2 p.m. on Monday, Oct. 14, in the Nursing Suite's lobby. The event aims to connect nursing students with local healthcare recruiters from major health systems.




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Crypto Price Today: Micro Losses Strike BTC, ETH Leaving Altcoins Turbulent

The overall crypto market cap tumbled by 4.12 percent over the last day due to market fluctuations. Bitcoin and Ether both registered losses on Wednesday. Tether, Solana, and Tron also saw registered losses alongside BTC and ETH. Ripple and Tron saw losses. 




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Desperate BCCI Schedules Practice Match For India. But, No One Can Watch

Team India is set to feature in an intra-squad warm-up game, starting Friday. But, fans won't be able to see the players in action.




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Traffic Rules: किस ट्रैफिक नियमों के उल्लंघन पर कितना है जुर्माना और चालान की रकम, जानिए डिटेल्स

Traffic Rules and Traffic Violation Fines in India: यातायात नियमों को तोड़ने वालों पर नकेल कसने के लिए दिल्ली में हाई-रेजोल्यूशन वाले AI-बेस्ड कैमरे लगाने की योजना पर काम किया जा रहा है.




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Secretary of State Orders Emergency Classification of Xylazine aka “Tranq” as Schedule III Controlled Substance

Delaware Secretary of State Jeff Bullock has placed xylazine, also known as “Tranq”— a non-opioid drug used primarily in veterinary medicine—in Schedule III of the Uniform Controlled Substance Act. Tranq has been used increasingly as an additive in opioid abuse to create a “zombie-like” condition for users. Secretary Bullock’s actions follow a recommendation from the […]




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Secretary of State Renews Emergency Order Placing Xylazine in Schedule III

Pursuant to 29 Del.C. §10119(3), Delaware Secretary of State Jeff Bullock has renewed an Emergency Order placing xylazine, also known as “Tranq”, temporarily in Schedule III in the state of Delaware. The Emergency Order took effect June 2, 2023, and was effective 120 days. The public threat posed by xylazine continues. Therefore, the renewal of […]



  • Department of State
  • Division of Professional Regulation
  • News
  • "Secretary of State"
  • Schedule III
  • Uniform Controlled Substance Act
  • xylazine

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Federal Court Rules Against Gun Lobby on Delaware Injunction

Delaware’s bans on assault weapons, large capacity mags remain in effect  A federal judge hearing a right-wing challenge against two common-sense gun safety measures in Delaware has ruled against the gun lobby on a critical question in Delaware State Sportsmen’s Association, Inc. et al. v. Delaware Department of Safety and Homeland Security et al.  In an […]



  • Department of Justice
  • Department of Justice Press Releases
  • News

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DOJ Secures Convictions For Two Delaware Women Who Claimed A Combined $114,815 In Fraudulent Tax Deductions

Two Delaware women have been sentenced to probation and suspended prison time for tax-related crimes after falsely claiming thousands of dollars in itemized deductions on their tax returns and submitting falsified documents during their respective audits. The cases represent the first prosecutions brought under the new initiative between the Department of Justice and the Department of Finance targeting state tax fraud “These convictions are the result of great work by our prosecutors and our […]



  • Department of Justice Press Releases

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Federal Court Rules for State, Against Gun Lobby on Landmark Gun Safety Law

A federal judge has denied another right-wing challenge to a commonsense gun safety law that allows gun dealers in Delaware to be held accountable in court for the violence they create.   This is Attorney General Kathy Jennings’ third consecutive legal win over the gun lobby.  Earlier this year, the same federal court ruled against plaintiffs challenging Delaware’s assault weapons ban and large-capacity magazine ban.  Both remain in effect, as well.  “Sometimes the facts of a case tell you all you need to know,” […]



  • Department of Justice Press Releases

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Attorney General Kathy Jennings supports new rules targeting money laundering

Attorney General Kathy Jennings has joined a coalition of 25 states and territories in filing a letter with the U.S. Treasury Department’s Financial Crimes Enforcement Network (FinCEN) in support of proposed rules entitled “Anti-Money Laundering Regulations for Residential Real Estate Transactions.”     The April 16 letter expresses staunch support for the would-be regulations, which will […]



  • Department of Justice Press Releases

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Unemployment Benefits Scheduled to Expire December 26, 2020

  FOR RELEASE: December 9, 2020 CONTACT: Kenneth Briscoe Kenneth.Briscoe@delaware.gov   Unemployment Benefits Scheduled to Expire on December 26, 2020 for Many Claimants in Delaware   WILMINGTON, DELAWARE – According to federal program guidelines, all unemployment compensation programs created by the CARES Act are currently scheduled to expire on or before December 26, 2020.   Many […]



  • Department of Labor
  • News

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Delaware Produce Farmers Encouraged To Attend Sessions On Proposed Rule Changes

The Food and Drug Administration (FDA) published a proposed rule change on December 6, 2021, to amend the agricultural water requirements of the Produce Safety Rule. In response to the proposed change, the Delaware Department of Agriculture and University of Delaware Cooperative Extension will host two outreach sessions on January 21, 2022, to engage farmers and other stakeholders.



  • Department of Agriculture
  • agricultural water
  • agriculture
  • Delaware Department of Agriculture
  • farmers
  • Food and Drug Administration
  • Food Safety Modernization Act
  • outreach
  • produce
  • Produce Safety Rule
  • proposed rule change
  • University of Delaware Cooperative Extension

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Scheduled Closure of the Office of Vital Statistics in Dover for Renovations

The Delaware Division of Public Health (DPH) announces that the Office of Vital Statistics (OVS) in Dover will be closed to the public for renovations beginning February 12 through April 5, 2024.



  • Delaware Health and Social Services
  • Division of Public Health
  • News

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Jennings can fight for Nemours funding, appeals court rules

A Florida appellate court has upheld AG Kathy Jennings’ authority to continue advocating for funding for Nemours Children’s Hospital. “The consequences of this case could be a game changer for kids in Delaware,” said AG Jennings. “Anyone whose child has received care at Nemours Hospital understands how exceptional they are. That’s the hallmark of A.I. […]



  • Department of Justice
  • Department of Justice Press Releases
  • News

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Scam Alert: Division Of Revenue Warns Taxpayers Of Fraudulent Letters

The Delaware Division of Revenue is warning the public of a new tax scam that’s happening in Delaware. Victims receive a letter from the “Tax Processing Unit” that threatens property seizure and wage garnishment unless the victim calls a toll-free number to “avoid enforcement.”



  • Division of Revenue
  • Scams
  • Tax Processing Unit

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601 Delaware Pesticide Rules and Regulations

DEPARTMENT OF AGRICULTURE: Office of the Secretary




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Rule 1008 (Formerly Rule 19.1) Bottle Clubs - Licensing and Operation

DEPARTMENT OF STATE: Office of the Alcoholic Beverage Control Commissioner




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Rule 702 (formerly Rule 51.1) A Rule Requiring the Biennial Renewal of Supplier's Licenses

DEPARTMENT OF STATE: Office of the Alcoholic Beverage Control Commissioner




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Rule 701 (Formerly Rule 51) A Rule Requiring the Biennial Renewal of Wholesale, Retail, and Annual Gathering Licenses

DEPARTMENT OF STATE: Office of the Alcoholic Beverage Control Commissioner




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601 (Formerly Rule 35.1) Gathering Licenses

DEPARTMENT OF STATE: Office of the Alcoholic Beverage Control Commissioner




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5001 Rules of the Office of the Marijuana Commissioner

DEPARTMENT OF SAFETY AND HOMELAND SECURITY: Office of the Marijuana Commissioner