This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page partnerships may have to file an Administrative Adjustment Request (AAR) While many are familiar with the historical process of amending returns the AAR process is much different and deserves a further look Although changing a return may be needed to correct an error it also may be needed to accomplish a certain goal many taxpayers have made legitimate employee retention credit (ERC) claims Many partnerships will need to file AARs as a result of these claims to reduce wage expense in accordance with the credit various tax bills may be on the horizon containing legislative changes that could be implemented retroactively AARs may be required to take advantage of or comply with these proposals The Bipartisan Budget Act of 2015 (BBA) was implemented to heighten compliance and transparency in the partnership tax space Generally applying to tax years 2018 onward unless the taxpayer can elect out of BBA rules they may need to file an AAR to change a previously filed return As an overarching rule, eligible partnerships to elect out of BBA must have 100 or fewer partners if one of these partners happens to be an S corporation the number of shareholders of that S corporation is included in the partner “count.” If the partnership has a partner listed as an ineligible partner in the below AARs are filed by the partnership wishing to change a previous tax return These changes can be categorized as “net positive” adjustments or “net negative” adjustments or reduce credits (and vice versa for net negative adjustments) There is a process of grouping and subgrouping changes and each subgrouping results in either a “net positive” or “net negative” result net positive and net negative adjustments cannot be netted An AAR can include both net positive adjustments and net negative adjustments Net negative adjustments must always be passed out to the partners of the year being changed the partnership may pay the tax on the net positive adjustments at the entity level This amount due is called the “imputed underpayment” (IU) the partnership may elect to “push out” the positive adjustments to the partners of the year being changed The partnership reports net negative adjustments or pushed-out positive adjustments to the partners using Form 8986 (functioning similarly to a Schedule K-1) If a partner is itself a pass-through (partnership it must continue to pass along the net negative adjustments from the lower tier AAR to its owners/beneficiaries and has the option to either push out or pay the IU associated with the net positive adjustments Certain complicating factors with pass-through partners exist but are outside the scope of this article Reach out to your advisor for more information One of the more unique aspects of AARs is their timing and how partners account for adjustments passed out to them the partners do not amend their returns for the changes they must recompute their Chapter 1 tax liability for the year being changed using the adjustments and account for the changes in Chapter 1 tax as either an increase or decrease to the Chapter 1 tax on their tax return that includes the date that the AAR partnership issued its Form 8986s a partnership needs to adjust its 2022 tax return (known as the “reviewed year”) to report additional ordinary income The partnership makes the election to push out the net positive adjustment it files the AAR and distributes Form 8986 to Partner A Partner A is an individual filing a calendar year return Partner A must recompute its 2022 tax return using the adjustments from Form 8986 and compare the adjusted tax to the tax on its original (or previously amended) 2022 tax return If there is a change to the 2022 Chapter 1 tax Partner A reports that change as an increase or decrease to its Chapter 1 tax on its 2024 tax return 2024 is the “reporting year,” as it includes the March 2024 date that the Form 8986 was distributed to the partners A reduction in tax from an AAR cannot reduce the reporting year Chapter 1 tax below zero which may result in a portion of the tax benefit from an AAR being permanently lost under existing rules The BBA regime only applies to Chapter 1 taxes (the most common example being income tax) etc.) must be adjusted to include adjustments made by the AAR but are not calculated or paid through the AAR or BBA examination process Deciding whether to push out the net positive adjustments or to pay an imputed underpayment is the first step in preparing an AAR Not only are there different forms to fill out and calculations to complete but there are also differences in potential tax due pushing out all adjustments is the favorable option the following discussion weighs the pros and cons of each option if there are any net negative adjustments after the grouping process the taxpayer must push out the net negative adjustment(s) to the partners Even if there are nine net positive adjustments and one net negative adjustment the partners must receive a Form 8986 with their portion of the one net negative adjustment it cannot use the negative adjustments as part of the tax calculation and thus it may be more tax efficient to push out the positive adjustments to the partners so that the negative adjustments may help reduce the tax paid overall to the IRS one benefit of paying the IU at the partnership level is that it avoids the partners having to report the adjustments and saves compliance costs This benefit does not exist if the partners are allocated negative adjustments and still have to recompute their reviewed year tax liabilities and report the change on the reporting year return partners may still have to amend their state income tax returns if the states do not have a similar process as the BBA process IUs are taxed at the highest current marginal tax rate (37% tax rate) This is regardless of the tax classification of the partners and if the change would have otherwise increased income and tax at the partner level positive adjustments that can impact the IU calculation can also include changes to an asset or liability balance on the partnership’s tax books and may be taxed at 37% (even though it could simply be a change in a balance sheet item that wouldn’t have impacted taxable income) the “preferential” capital gains rate that individual partners may benefit from is disregarded a “modification” process is possible in limited situations to adjust the 37% rate This modification process can be time-consuming and complicated especially if there are multiple tiers of pass-through entities in the ownership chain A push-out election would allow the partner to calculate the change in tax due using their individual tax situation if they would have been afforded a 20% capital gains rate on their Form 1040 for the additional income the 20% rate would apply when determining the change in tax for their Form 8978 that would offset an increase to income from Form 8986 Section 199A is a deduction put in place by the Tax Cuts and Jobs Act of 2017 (TCJA) to benefit individual and trust taxpayers who are allocated pass-through income if there is an increase in ordinary income there is also an increase in §199A income reported to partners This then provides the opportunity for a higher deduction at the partner level The same mechanics would be possible with the push-out election but by paying an IU instead the benefit is lost There may be changes that directly result from the “core” adjustment in the AAR an increase in ordinary income may also affect excess taxable income (ETI) calculated as part of the §163(j) interest limitation within the partnership return Each change would be listed as a separate subgrouping for the IU The taxpayer is taxed twice for effectively the same change it may be possible to treat certain adjustments as zero for the IU calculation if one adjustment is reflected in one or more other partnership adjustments (anti-duplication provisions) Even though partners receiving a Form 8986 will account for changes later than the partnership would pay the IU this does not necessarily mean interest has to accrue on the changes for a longer period of time the partner does not have to wait to pay the additional tax due with the reporting year return but can prepay the additional tax and thus “cut off” the interest accrual on AAR changes Let’s say the partnership is adjusting a 2021 tax return via AAR both Partner A and Partner B each owned 50% of the partnership the partnership realizes that an AAR should be filed for 2021 Partner B transferred its entire interest to Partner C the Forms 8986 are sent to the partners that were present in the reviewed year The changes are also allocated according to the operating agreement as in effect for the reviewed year Partner A and Partner B would receive 50% of the changes on Forms 8986 to be accounted for on their 2024 tax returns via Form 8978 If the partnership instead chooses to pay the IU the “economic burden” of 50% of the IU payment is felt by Partner C there is a grouping process that the changes within an AAR must go through The result of this grouping process can cause some unusual results if paying the IU: AARs can often feel like a burdensome process, and it can take time to complete them correctly. However, with ERC and upcoming possible legislative changes, there may be more and more reasons to file AARs in the coming years. Our knowledgeable tax team can help you through the whole AAR process and answer any questions you may have about your options please reach out to a professional at Forvis Mazars About  .  Contact  .  Donation which experts believe dates back to around 2000 BCE was at first thought to be a row of post holes excavation leader Andreas Bo Nielsen and Vesthimmerlands Museum curator Sidsel Wåhlin soon recognized its true importance Experts have found similar wooden circles in Britain These structures are often linked to sun worship and agricultural rituals Experts still argue about its exact purpose The Danish woodhenge seems to align with Stonehenge and the nearby Woodhenge This hints that Neolithic communities across Europe might have shared religious or cultural beliefs Wåhlin said this find shows a strong connection to British henges She added that researchers are now looking to see if there’s an inner circle inside the structure The settlement included a chieftain’s grave and a bronze sword which also shows the area was important to ancient people Experts are now conducting a sampling exercise to study the wood and look for “ritual deposits,” such as flint arrowheads and daggers they could tell them a lot about the people who built the structure and what they believed Archaeologists have found similar wooden circles on Bornholm Wåhlin said that the Aars structure is “the first one of this larger type that we can investigate.” Studies indicate that Britain saw a big demographic shift around the time people built Stonehenge after groups migrated from Central Europe and the Steppes Some experts think that buildings like Stonehenge and its newly found Danish counterpart might have helped bring early farming communities together and strengthen shared beliefs Researchers plan to analyze DNA from wood pieces found at the location to examine possible genetic connections between early populations in Denmark and website in this browser for the next time I comment Δdocument.getElementById("ak_js_1").setAttribute("value",(new Date()).getTime()) Learn how to describe the purpose of the image (opens in a new tab) Leave empty if the image is purely decorative Our latest Archinect Studio Pin-Ups takes a look at three studios at Archinect Partner School USC School of Architecture offered as part of their one-year Master of Advanced Architectural Research Studies (M.AARS) postgraduate program The results showcase the greater need for deep sustainability and more inclusive and democratic economic systems A report was produced as part of one studio and students learning under Sulzer's Spring 2024 offering collectively designed a 1-1 intervention using the adaptive p/re-use design ideas they produced in the previous term *Are you an instructor or current architecture student participating in an exciting studio? We are accepting submissions for our Archinect Studio Pin-Ups series. Reach out to us here for a chance to be featured Project One: 'Alleys for All' by Hunter Barnett Description: "As one of the city’s — and nation’s — densest occupied neighborhoods Koreatown lacks amenities and usable public spaces to adequately accommodate its population Koreatown features an abundance of underutilized ‘Alleys for All’ attempts to create a framework that enables both the city and the adjacent property owners to transform these alleys into accessible multi-functional public and community spaces Bolstering both private and public interests the project envisions designing open structures as public infrastructure (and public investments) allow the community to use the alleys as shaded public space or gardens and the property owners to attach commercial spaces The structures’ modular and open design is further geared towards collecting water and accommodating energy infrastructure such as solar panels that could serve the whole residential block." Description: "'Revitalizing Wilshire' addresses the lack of activity along Koreatown’s once lustrous Wilshire corridor Although many unoccupied or underutilized spaces hide in plain sight K-Town’s Wilshire Boulevard has a rather high rate of vacancy dozens of unoccupied buildings on and around Wilshire are either slated to be demolished Given that many of these soon-to-be-demolished buildings possess diverse materiality and other intriguing bits of character 'Revitalizing Wilshire' looks to reusing and recontextualize these ‘demolition’ elements on selected buildings and junctions along the boulevard creating a series of architectural palimpsests that exalt the rich character of K-Town’s built environment the junctions and buildings will be transformed and adapted to provide the community with four distinct yet equally crucial programs Managed and operated by a '4-in-1 Non-Profit' structure owned by community members the reactivated and revitalized structures will accordingly offer affordable retail space Project One: 'Zoup(ing) LA' by Joshua Ryan Description: "Addressing the affordable housing and commercial real estate crisis 'Zoup(ing) LA' proposes a change in state and local zoning laws that would allow more flexible and comprehensive ways to make use of gaps or left over spaces within the urban fabric Combining the words Zone (specific purpose) and Soup (blend) the term ‘Zoup’ is defined as the opposite of a zone; the act or process of blending urban infill and live/work opportunities into a comprehensive urban fabric A set of new Zoup policies envision a different take on how to produce housing and the urban fabric: unlocking underutilized land tax incentives for non-speculative co-operative housing flexibility for previously separated uses to enable a blend of live/work/production/commercial setups allowing for incremental construction and planning and implementing incentives for using repurposed and recycled materials Applying these policies in the neighborhood of Venice the Zoup(ing) LA proposes a construction co-operative which produces an architectural kit of parts that can flexibly and adaptively fill in existing underutilized parcels with affordable housing Project Two: 'From Forest to Framework' by Ellie Selzer Description: "'Forest to Framework' seeks to re-frame the framework of sustainably harvested mass timber products and show how they can be utilized in design practices to maximize flexibility It is vital that timber products used in the construction industry are sourced from sustainable certified forest lands to ensure that deforestation of green reserves is mitigated The existing supply chain is not vertically integrated and it follows the cradle-to-grave pipeline where building materials most likely end up in landfills following demolition The industry should therefore introduce a closed-loop product life cycle system using the cradle-to-cradle concepts introduced by architect William McDonough The main priorities within this system are to ensure the increase in sustainable land management practices to grow the demand for sustainably harvested and produced mass timber products and to create deconstruction and reuse toolkits that can be adopted into standard design and construction practices Applying this framework to an affordable housing cooperative located in Venice Beach this system of flexible and deconstructable mass timber members creates a community of spaces for users to grow their own nutrients as well as their own houses within a diverse community." Project One: 'Open Source Housing' by Boyuan Wu Description: "'Open Source Housing' proposes a transformative model for affordable and sustainable housing delivery Inspired by existing models of open-source design and production — such as WikiHouse — Open-Source Housing goes beyond offering an open decentralized process: it aims at integrating its open-source production tool kit into an incremental and radically circular housing delivery scheme Using the Community Land Trust (CLT) and Limited Equity Co-operative (LEC) models Open Source Housing not only establishes a CLT to extract land from speculation and lease it back to its trust members at an affordable price It also establishes a LEC that integrates all produced and used materials into a leasing system where the building materials are considered part of a revolving pool of resources that will return to the LEC after disassembly to be reused or recycled Open Source Housing will open up possibilities for a diversity of owners and inhabitants to participate in the production of a multitude of ecological and affordable housing solutions applied at different scales and adapted to various contexts." Description: "'Practopia' proposes a concept of urban transformation that is both pragmatic and reminiscent of utopian ideas of collective living Practopia seeks to introduce new affordable multifamily housing as well as micro-commercial programs to foster a more resilient Building on the hybrid ownership structure of the Community Land Trust (CLT) model Practopia envisions a framework for participation as well as non-speculative housing options Practopia itself is a hybrid: creating pragmatic improvements for inhabitants and owners who join the CLT and advocating for utopian ideas for collective living at the same time and community-centric future of a Koreatown block Description: "'Food-Play-Learn-Recycle' is the result of applying the notion of Adaptive R/Re-use into action through a 1-1 scale design-build project within the neighborhood of Koreatown Students were tasked to design a project built with reused materials and able to be disassembled as well as be adapted for other potential uses No new building materials were purchased: they were scavenged on campus and collected within the neighborhood of Koreatown Based on the resulting inventory and developed digital library of reclaimed materials students engaged in a collective design process to develop a 1-1 intervention The resulting ‘Food-Play-Learn-Recycle’ pavilion addressed three major neighborhood challenges: a lack of affordable and healthy food The pavilion was installed in front of — and in collaboration with — KYCC The students developed a ‘waste for food’ concept where local youth was encouraged to deposit recyclable materials while using the possibilities to play chess and is now waiting for a future use and application yet to be determined." Studio Instructors: Sascha Delz and Julia Sulzer Coordinator M.AARS City Design + Housing: Sascha Delz Learn more about USC School of Architecture and past editorial coverage by exploring their Archinect School Profile Josh Niland Josh Niland is a Connecticut-based writer and editor. He studied philosophy at Boston University and worked briefly in the museum field and as a substitute teacher before joining Archinect.  He has experience in the newsrooms of various cultural outlets and has published writing ... Alexander Walter Alexander Walter grew up in East Germany with plenty of Bratwurst. He studied Architecture and Media Design at Bauhaus-Universität Weimar, Germany, and participated in foreign exchange programs with Washington-Alexandria Architecture Consortium in Alexandria, Virginia and Waseda University in ... Are you sure you want to block this user and hide all related comments throughout the site Your comment will be visible once approved Join the news democracyWhere your votes decide the Top 100 Reasons for you to sign up to our newsletter here Archaeologists in Denmark have uncovered the “Danish Stonehenge” in what has been called a “once in a lifetime find” The discovery of a circular formation of wooden piles date back to around 2,000 BC and Danish archeologists say they have a “strong connection” to the famous prehistoric Stonehenge structure in the UK The 4,000-year-old 45 neolithic-era wooden pieces arranged in a 100-foot-diameter circle and around 2 metres apart were found accidentally during work on a housing estate in the town of Aars conservationist at the Vesthimmerland museum in Aars “It is a once in a lifetime find” and added that the circle “points to a strong connection with the British henge world” The two circular structures at Stonehenge – which feature a small circle surrounded in a horseshoe shape by a larger one – were thought to have been erected sometime between 3100 BC and 1600 BC work is now being undertaken to establish whether a smaller inner circle exists in a similar fashion “When I and my colleague opened a new section of the excavation the expected house and some fence quickly turned out to be the entrance area of a very well planned some timber circles involved in the practice of worshipping the sun have been found on the Danish island of Bornholm the recent discovery is “the first one of this larger type that we can properly investigate” Before the discovery of the 45 wooden pieces archaeologists uncovered an early Bronze Age settlement In the settlement was a chieftain’s grave and a bronze sword Moon filmed in incredible detail by lunar lander spacecraft Space discovery shows the pyramids were built using ingenious method Sign up for our free indy100 weekly newsletter How to join the indy100's free WhatsApp channel Click the upvote icon at the top of the page to help raise this article through the indy100 rankings Danish archeologists have uncovered a 4,000-year-old circle of wooden piles that they say could be linked to Britain's world-renowned Stonehenge in a circle with a diameter of about 30 meters (100 feet) were found during work on a housing estate in the northwestern town of Aars The circle "points to a strong connection with the British henge world," she added The two circles of stones at Stonehenge in southern England are believed to have been erected between 3100 BC and 1600 BC The Danish archeologists are now trying to find if there is an inner circle at the Aars site have been found on the Danish island of Bornholm She added that the circle in Aars was "the first one of this larger type that we can properly investigate" Archeologists first found an early Bronze Age (1700-1500 BC) settlement at the building site that included a chieftains grave and a bronze sword "When I and my colleague opened a new section of the excavation the expected house and some fence quickly turned out to be the entrance area of a very well planned The wooden circle is estimated to date from about 2000 BC but Wahlin said the team had started detailed work on Monday to definitively identify its age and function The archeologists are now looking for "ritual deposits" such as flint arrowheads and daggers as part of a major sampling exercise at the site Wahlin said the next searches would seek to find if there were links between the region and other peoples She said the influence of other regions could be seen in the pottery and graves that had been found © Agence France-Presse A recent study by RP Legal Group identified Louisiana as the US state with the highest rate of medical malpractice over the last decade while Hawaii ranked as the state with the lowest rate based on data from the National Practitioner Databank (NPDB) between 2013 and 2023 analyzed adverse action reports (AARs) against healthcare providers across the US Louisiana topped the list with 28.55 AARs per 100,000 people The year 2015 saw the highest number of cases in the state Louisiana experienced an 18 percent decrease in reports over the period analyzed Wyoming followed closely with a rate of 26.18 per 100,000 people Although Wyoming’s AAR count had declined by 29 percent since 2013 2023 marked the lowest number of reports in Wyoming Colorado ranked third with a rate of 25.6 AARs per 100,000 people seeing a 15 percent increase in the number of reports over the decade Colorado reached its peak in 2018 with 2,022 reports experienced a significant decrease of 42 percent in AARs between 2013 and 2023 despite having a rate of 22.92 per 100,000 people Rounding out the top five states was Oklahoma with an average annual rate of 22.50 AARs per 100,000 people Oklahoma saw the most substantial decline among the top states with a 77 percent drop in reports filed over the decade Hawaii had the lowest rate of medical malpractice The state averaged 62 reports annually and saw a 39 percent decline since 2013 New York reported a rate of 5.46 per 100,000 people but experienced a 52 percent decrease in reports Commenting on these findings, Robert Rikard from RP Legal Group emphasized the importance of addressing systemic issues within healthcare there were 26,805 reports filed throughout America with Texas having the highest number of reports at 2,870 These figures indicate an issue within healthcare systems and protocols that must be revisited to prevent malpractice.” Rikard pointed out that medical malpractice could arise from various factors stressing that “healthcare workers must ensure they have thorough training and stay up to date with advances in the healthcare system to reduce potential malpractice.” The analysis highlighted the importance of consistent training and oversight in the healthcare system to address and prevent cases of malpractice that could have severe consequences for patients A union grievance protesting the publication of “Adverse Action Reports” (AAR) by the Department of Veterans Affairs (VA) resulted in an arbitration decision directing VA to remove AARs from its website and to cease and desist the publication of AARs the VA has published AARs on its website that provide visitors to the website with information regarding disciplinary actions taken against VA employees The American Federation of Government Employees (AFGE) filed a grievance alleging that the compilation and publication of the information contained in the AARs violated the Privacy Act The arbitrator’s decision follows the evolution of the VA’s disciplinary tracking system used to share information internally about employee discipline which was initially created as an ad hoc “computerized information sharing site” that received inputs from all VA offices on every instance of employee discipline Offices were expected to report extensive information about the nature and timing of the disciplinary action When the decision was made to publish AARs the now-defunct Office of Accountability Review (OAR) “scrubbed” the tracker of some information When OAR was replaced by the Office of Accountability and Whistleblower Protection (OAWP) the tracker was replaced with a new database called “HRSmart.” HRSmart’s database also tracked Employee Identification Numbers (EIN) in addition to the previously tracked information though those EINs were not published in the AAR Concerns regarding the ease with which employees could be identified proliferated despite purported efforts by OAWP to sanitize the disciplinary records and testimony by OAWP officials at the arbitration revealed that the AAR gave rise to employee privacy complaints and had a negative effect on employee morale.  VA argued that publication of the AAR could not violate the Privacy Act because the information contained within the AAR did not constitute “records” within the meaning of the Privacy Act The arbitrator concluded that Tobey suggested that the disputed information was appropriately viewed as a Privacy Act “record” because it was information about “not just the issuance of discipline but about specific instances of discipline issued to particular individuals who in some instances can be particularly identified by the published information notwithstanding the Agency’s effort to scrub or sanitize the data set.” The arbitrator therefore found that VA’s publication of the AAR was a disclosure of Privacy Act “records” that were “about” particular employees and that his finding was consistent with a previous VA General Counsel Advisory Opinion from March 14 That Advisory Opinion held that “Under the Privacy Act on its own initiative and without prior written consent disclose information about disciplinary actions against identified management officials…Information about disciplinary actions cannot contain details which would allow employees including employees at the involved facility to identify the disciplined employee.” The arbitrator noted that the VA “flagrantly disregarded the Agency’s own General Counsel’s advisory opinion and the rights of those employees whose particular work circumstances allowed them particularly to be identified.” Although the VA’s “purpose” in publication of the AARs was to “rehabilitate its public image” rather than to disclose the identity of any particular employee the arbitrator found that this goal “in no way detracts from the fact that the disclosures themselves were willful and intentional taken with a known risk that publication of such information could lead to privacy violations as recognized by the Agency’s witness and its own General Counsel’s advisory opinion.” In addition to finding that publication of the AARs violated the Privacy Act the arbitrator also found that the VA violated two separate articles of its collective bargaining agreement with the union The arbitrator also found that unilateral publication of the AARs constituted an unfair labor practice because the VA had a statutory duty under 5 U.S.C § 7116(a)(1) and (5) to “bargain with the Union over changes in the terms and conditions of employment that are more than de minimis.” the arbitrator directed the VA to “remove the AARs from its website and cease and desist publishing the AARs in that or like manner until such time as it achieves compliance with the Privacy Act Read the full opinion: FMCS Case No. 17-54365 This case law update was written by Conor D. Dirks, Associate Attorney, Shaw Bransford & Roth, PC has provided superior representation on a wide range of federal employment law issues from representing federal employees nationwide in administrative investigations to handling security clearance adjudications and employment discrimination cases ABOUT CONTACT ADVERTISE PRIVACY POLICY DISCLAIMER Metrics details Protein translation is the ultimate paradigm for sequence-defined polymer synthesis To introduce non-canonical monomers into the genetic code of living organisms pairs of biomolecules known as aminoacyl-tRNA synthetases (aaRSs) and transfer RNAs (tRNAs) are required The discovery and engineering of five such pairs that do not interfere with each other or the aaRS–tRNA pairs of a bacterial host sets the stage for highly modified genetically encoded biopolymers Prices may be subject to local taxes which are calculated during checkout A review about sequence-defined synthesis of artificial polymers in cells Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA This article presents the discovery and characterization of the PylRS–tRNAPyl pair Mutually orthogonal pyrrolysyl-tRNA synthetase/tRNA pairs This article describes the generation of mutually orthogonal PylRS–tRNAPyl pairs Engineered triply orthogonal pyrrolysyl–tRNA synthetase/tRNA pairs enable the genetic encoding of three distinct non-canonical amino acids This article reports the engineering of triply orthogonal PylRS–tRNAPyl pairs used to incorporate three distinct ncMs into a protein A 68-codon genetic code to incorporate four distinct non-canonical amino acids enabled by automated orthogonal mRNA design This article describes the genetic encoding of four distinct ncMs into a protein Download references Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations This is a summary of: Beattie, A. T. et al. Quintuply orthogonal pyrrolysyl-tRNA synthetase/tRNAPyl pairs Nat. Chem. https://doi.org/10.1038/s41557-023-01232-y (2023) Reprints and permissions Download citation DOI: https://doi.org/10.1038/s41557-023-01262-6 Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Volume 10 - 2022 | https://doi.org/10.3389/fbioe.2022.918659 This article is part of the Research TopicCell-Free Synthetic Biology, Volume IIView all 16 articles Cell-free biology is increasingly utilized for engineering biological systems and circumventing many of the complications associated with cells The central dogma describes the information flow in biology consisting of transcription and translation steps to decode genetic information Aminoacyl tRNA synthetases (AARSs) and tRNAs are key components involved in translation and thus protein synthesis This review provides information on AARSs and tRNA biochemistry summarizes progress in cell-free engineering of tRNAs and AARSs and discusses prospects and challenges lying ahead in cell-free engineering Initially, cell-free systems were prepared using cell lysates, where cells were lysed, chromosomal DNA and cell membrane debris were removed, and the rest of the cellular contents were used for studies. Lysate-based systems suffered from batch-to-batch variation, hampering the ability to obtain consistent results (Hunter et al., 2018; Dopp, Jo, and Reuel, 2019) These systems also often contained inhibitory factors and in the context of molecular engineering of fundamental importance lysates are complex and their composition is unknown and the focus of this review lies on aminoacyl tRNA synthetase and tRNA biochemistry and engineering in the context of cell-free systems Genetic information in biology is decoded through transcription and translation steps to result in RNA and proteins Scientific activities in the last century helped us reach our current understanding of the steps involved in processing genetic material a brief history of the discovery of key steps and components involved in the central dogma is discussed the scientific community believed that proteins should be the genetic material as they are structurally diverse being made from 20 different building blocks nucleic acids have only 4 bases as their building blocks and were thus thought less likely to be the carrier of genetic information The genetic code linkage between nucleic acids and proteins was discovered by Marshall Nirenberg in 1961 (Nirenberg and Matthaei, 1961) Nirenberg’s work showed that codon triplets of RNA gave rise to amino acid sequences during protein synthesis This work laid the foundation for establishing the codon–amino acid relationship in protein synthesis which is referred to as the second genetic code Many components are required to implement the genetic code and key components are DNA Genetic code implementation is a result of specific interactions between these components There is a nucleotide-based world (DNA and RNA) and an amino acid–based world (proteins) DNA replication duplicates and maintains the genetic code The transcription step results in single-stranded RNA molecules using DNA as its template and the translation step uses RNA as its template to synthesize protein peptides and completes the decoding of genetic information The translation process bridges the nucleotide world and the amino acid world Now we know that AARSs are the enzymes responsible for charging cognate amino acid onto its cognate tRNA The fidelity of the translation process is hugely dependent on the specificity of the AARS enzymes These enzymes have a direct influence on the protein synthesis process segregating proteogenic amino acids from non-proteogenic amino acids The next section contains details on tRNAs and AARSs focusing on synthesis This section focuses on providing basic information on the structure and the role of tRNA and AARS in the protein synthesis process coli AARSs and tRNAs unless otherwise indicated Structure of tRNA presented in the 2-D cloverleaf model (left) and in the 3-D “L” shaped model (right) The tRNA consists of acceptor stem (green) The number of tRNAs present in an organism is dependent on codon usage there are 64 (43) different codon sequences available and UGA) are called stop codons and do not have a corresponding tRNA These 61 tRNAs are shared amongst 20 amino acids The number of tRNA acceptors for each amino acid is not the same and varies across amino acids there exists only one tRNA for the amino acid methionine with codon AUG multiple tRNAs can carry the same amino acid at their 3’ end and such tRNA groups are referred to as isoacceptors there are six isoacceptor tRNAs for the amino acid lysine with codons UUA AARS binds to the ATP and amino acid to form an aminoacyl intermediate the amino acid is transferred onto tRNA resulting in activated tRNA being ready for the translation process AARS becomes free for the next cycle of aminoacylation (B) Depicting the molecular structure of terminal adenosine of tRNA and the attack of the hydroxyl group (2′/3′) in AA-AMP intermediates ATP and amino acid bind to the AARS enzyme triggering a nucleophilic attack of the amino acid carboxyl oxygen to the α-phosphate group of ATP This results in amino acid adenylate intermediate (AA–AMP) and release of pyrophosphate (PPi) one of the hydroxyl groups of adenosine (3′-OH/2′-OH) in tRNA attacks the carboxyl carbon of AA–AMP intermediate resulting in the transfer of amino acid to tRNA The amino acids and tRNAs are linked by an ester bond which are released from the catalytic site of the enzyme and the AARS enzyme is free for the next cycle tRNA is not required but some AARSs such as GlnRS and class I LysRS require tRNA as a prerequisite for amino acid activation Activated tRNA-AA binds with the elongation factor and when reaching the ribosome participates in translation the cognate amino acid is selected by its ability to interact with zinc ions present in the active site whereas non-cognate amino acids fail to do so List of tRNA identity elements and their location on tRNA for aminoacylation by AARS from E Identity elements for fMet are provided in italics and bold AARSs are grouped based on the location of the identity elements present on tRNA regions The list of AARS under each group and the tRNA bases utilized for recognition are highlighted Additional discrimination comes from the kinetic aspect of binding to discriminate cognate tRNAs. Aminoacylation with cognate tRNAs is more influenced by Kcat values than KM values (Ebel et al., 1973) Evolutionary conservation of the identity elements in tRNAs suggests their importance even though these elements do not directly contribute to protein synthesis Pauling in 1958, theoretically predicted that amino acid misincorporation during translation should be about 1 in 200 (Pauling, 1958). However, in vivo experiments showed that this error rate is about 1 in 3,000 (Loftfield, and Vanderjagt, 1972) Aminoacylation by AARS has an error rate of about 1 in 10,000 This led to the suggestion of some editing mechanism being in place to account for these observations The low error rate for AARSs is due to better recognition of cognate substrates and a proofreading/editing mechanism This section briefly describes the editing/proofreading mechanism used by AARSs to ensure faithful aminoacylation de-acylation of cognate amino acid is prevented as it cannot enter the editing site Evidence for the presence of a separate editing site is seen in 10 AARS from both classes I and II Editing activity can be divided into pre-transfer editing and post-transfer editing editing occurs before the amino acid is transferred to tRNA editing occurs after the amino acid is transferred to tRNA Most AARSs use one of these editing mechanisms but some AARS such as LeuRS and ValRS use both mechanisms Pre-transfer editing occurs after the formation of amino acid adenylate (AA–AMP) but before transfer to tRNA Pre-transfer editing is seen in both AARS classes Pre-transfer editing can occur in two methods AA–AMP is released by the enzyme to the cytosol and the phosphoester bond is spontaneously hydrolyzed enzymatic hydrolysis of AA–AMP occurs either in the active site or in a separate editing site thiolated non-proteogenic amino acids such as homocysteine and ornithine are cleared by pre-transfer editing in the active site of the enzyme by MetRS and LysRS Post-transfer editing occurs after the transfer of amino acid to tRNA and occurs in a separate editing site This editing involves cleaving the ester bond between amino acid and tRNA amino acid triggers a conformational change in the 3′ end of tRNA and results in tRNA translocation Translocation results in an amino acid being in the editing site where it is hydrolyzed mischarged tRNA is rapidly released and in those cases enzymes are capable of recapturing these mischarged tRNA for editing PheRS competes for Tyr-tRNAPhe with EF-TU to recapture and edit the tRNA The preference for the editing mechanism used is dependent on the rate of amino adenylate hydrolysis and transfer to tRNA In case of a faster transfer rate to tRNA as in ValRS both reaction rates are fairly equal and hence both editing mechanisms are used Editing mechanism for aminoacylation process Pre-transfer editing occurs before amino acid gets charged onto tRNA Post-transfer editing occurs after amino acid is charged onto tRNA Trans editing factors are independent editing proteins involved in hydrolysis of mischarged tRNA The accuracy of protein synthesis relies on an AARS's ability to recognize cognate amino acids and tRNAs Kinetic analysis is useful to develop the mechanism of action in the steps involved in aminoacylation This section provides information about different kinetic approaches used to study tRNA aminoacylation The parameters widely used to describe the kinetics of AARSs are substrate affinity KM KM refers to affinity of the enzyme to the substrate Kcat is the catalytic constant for substrate to product conversion Kcat/KM is the specificity constant or catalytic efficiency of the enzyme Steady-state kinetics is useful for initial characterization of the enzyme and to measure kinetic parameters Since steady-state kinetics are used generally parameters obtained can be compared across systems enzyme specificity for cognate and non-cognate amino acids can be measured and compared across AARSs Steady-state measurements are usually performed with substrate concentrations much higher than enzyme since the assay follows product formation Minimal material requirements and fast readout make the steady-state approach suitable for initial characterization The drawback of steady-state kinetics is that elementary reactions cannot be characterized To determine the rate of the aminoacylation process ATP pyrophosphate exchange assays and aminoacylation assays are performed under steady-state kinetics The ATP–PPi exchange assay is based on the amino acid activation step ATP and amino acids form aminoacyl adenylate intermediate (AA–AMP) with the release of pyrophosphate (PPi) The radioactive group reacts with AA–AMP resulting in [32P]-ATP This assay measures the exchange of [32P]-PPi into ATP to provide rate of the activation step radioactive [32P]-ATP is used for amino acid activation and the rate of ATP consumption is measured using activated charcoal or thin layer chromatography (TLC) plates KM and Kcat values of amino acids for AARS from E Unit for Kcat is s−1 unless mentioned otherwise Pre-steady state kinetics is used to study elementary reaction steps The pre-steady state kinetic approach is used to study fast reactions present at an early stage of the interaction This approach is best for understanding the mechanistic action of interaction Parameters like individual rate constants of the reactants can be determined using pre-steady state kinetics substrate-binding order in the active site and consumption of intermediates can be studied by pre-steady state kinetics Rapid chemical quench and stopped-flow fluorimetry are generally used to study AARSs Rapid kinetic approaches were used to mechanistically distinguish the two classes of AARSs product release of AA-tRNAaa is the rate-limiting step amino acid activation is the rate-limiting step Rapid chemical quench is a discontinuous assay providing a direct readout of the rate of the radiolabeled product formed Stopped-flow fluorimetry is a continuous assay and provides an indirect readout of reaction progress Progress is dependent on changes in intrinsic tryptophan fluorescence correlated to reaction chemistry Table 3 contains the half-life of activated tRNA-AA measured in E. coli (Hentzen, Mandel, and Garel, 1972) The value represents the spontaneous hydrolysis rate of tRNA-AA at neutral or alkaline pH in a high ionic condition at 37°C the stability of the ester bond depends purely on the amino acid attached to tRNA Half-life for all amino acids but tryptophan is presented and ranges from 2 to 65 min TABLE 3. Half-life values of tRNA-AA from E. coli. Values obtained based on ester bond hydrolysis under neutral or alkaline pH in a high ionic medium at 37°C (Hentzen, Mandel, and Garel, 1972) Orthogonal pairs TyrRS/tRNA-Tyr obtained from archaea Methanococcus jannaschii and pyrrolysyl-(Pyl)RS/tRNA-Pyl from Methanosarcina barkeri are most commonly used for incorporating NC-AAs The open nature of cell-free protein synthesis (CFPS) provides a higher degree of freedom for structurally and functionally diverse NC-AAs to be incorporated and cross membrane transport are not constraints for CFPS allowing incorporation of many different NC-AAs Charging of orthogonal tRNA with NC-AAs is a key step in the translation process and it is usually mediated by AARS enzymes there are other methods such as the chemoenzymatic method and ribozyme-based approaches for acylation to charge tRNA with NC-AAs These synthetic methods are utilized in vitro to generate pre-charged tRNAs with NC-AAs and can be directly supplemented into the cell-free system Such pre-charged tRNAs are useful to learn more about single turnover translation The key advantage of chemical acylation methods is that structurally and chemically diverse groups can be added onto tRNAs without the need to re-engineer AARS this approach does suffer from low efficiency and therefore yield they will compete with the same codon and lower the incorporation of NC-AAs the relative ratio of NC-AA to cognate amino acid should be tightly controlled to favor NC-AA incorporation However site-specific incorporation requires a faster and more accurate aminoacylation reaction between NC-AA and tRNA there is a need for a better strategy to identify mutants with better incorporation efficiency Many functional groups can be ligated to tRNA with this approach but it is cumbersome due to the laborious chemical process involved in the preparation of acylated nucleotides Different aminoacylation methods used for NC-AA incorporation Cell-free transcription and translation systems have enormous potential to overcome the limits of cell-based protein synthesis and could become the next generation platform for protein engineering that can go well beyond the scope of what could be accomplished in a cellular environment This work was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program Grant 723106 and a Swiss National Science Foundation grant (182019) Open access funding provided by École Polytechnique Fédérale de Lausanne The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher Analysis of the Kinetic Mechanism of Arginyl-tRNA Synthetase Biochimica Biophysica Acta (BBA) - 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Ganesh RB and Maerkl SJ (2022) Biochemistry of Aminoacyl tRNA Synthetase and tRNAs and Their Engineering for Cell-Free and Synthetic Cell Applications Received: 12 April 2022; Accepted: 18 May 2022;Published: 01 July 2022 Copyright © 2022 Ganesh and Maerkl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Sebastian J. Maerkl, c2ViYXN0aWFuLm1hZXJrbEBlcGZsLmNo Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish. Danish archaeologists have discovered a 4,000-year-old wooden circle in the town of Aars, in northwestern Denmark, which might be related to Britain’s Stonehenge. Archaeologists made this discovery during construction work on a housing estate. As per GB News, experts believe the ancient structure could provide evidence of a historical link between Neolithic people in Denmark and Britain. The discovery includes 45 wooden pieces from the Neolithic era, arranged in a circle with a diameter of about 30 meters. The wooden pieces create a slightly oval-shaped structure, with each piece placed about two meters apart. Sidsel Wahlin, conservationist at the town's Vesthimmerland museum, said "It is a once in a lifetime find.” She added that the circle "points to a strong connection with the British henge world." Archaeologists are now examining the site to see if it has an inner circle, like the concentric design of Stonehenge. Experts mentioned that similar wooden circles, believed to be linked to sun worship, have been found on the Danish island of Bornholm. Wahlin pointed out that the Aars circle is the first large one that can be properly studied. The Danish wooden circle is estimated to be from around 2000 BC. Moreover, the timing suggest that the wooden circle and Stonehenge might have been constructed around the same historical period. Volume 15 - 2024 | https://doi.org/10.3389/fneur.2024.1376643 This article is part of the Research TopicConsanguinity and Rare Genetic Neurological DiseasesView all 9 articles The intricate relationship between seizure control and cognitive impairment remains complex an intensified form often rooted in genetic factors is detectable through next-generation sequencing We present a case involving two sisters with refractory generalized seizures evolving into dysarthria abnormal electroencephalogram results consistent with epilepsy were noted Whole Exome Sequencing identified heterozygous variants in the alanyl-tRNA synthetase (AARS) and Calcium Voltage-Gated Channel Subunit Alpha 1 (CACNA1A) genes Patients A and B exhibited a unique blend of neurological and psychiatric conditions distinct from common disorders that begin adolescence Whole Exome Sequencing uncovered an AARS gene and CACNA1A gene linked to various autosomal dominant phenotypes coupled with familial reports of migraines and seizures provides insight into accelerated symptom progression This study underscores the importance of genetic testing in decoding complex phenotypes and emphasizes the value of documenting family history for anticipating related symptoms and future health risks Understanding the intricate relationship between genetic factors and channelopathies in epileptic encephalopathy is crucial for precise diagnosis along with abundant multifocal epileptic activity and generalized activity Cerebral magnetic resonance image did not show structural lesion the patient was highly dependent and required assistance with her daily living activities like bathing (A) Electroencephalogram of patient A with a bipolar montage showed generalized slowness in the background activity Electroencephalogram showing reported generalized slowness of background activity with abundant multifocal epileptic activity predominantly affecting the posterior regions consistent with a non-convulsive status epilepticus (C) Electroencephalogram in normal conditions showed generalized slowness in the background activity the patient was dependent and required assistance with her daily living activities like bathing We conducted a Whole Exome Sequencing (WES) analysis on the peripheral blood samples obtained from both the sisters and their parents to ascertain the genetic condition The parents were not consanguineous but were born and live in the same rural area The father had migraine and memory impairment during adolescence Relatives from the father side have seizures We used a capture of target regions using probes followed by next-generation sequencing with Illumina technology whereas that of the mapped reads was 41,603,016 (99.86%) We aligned the raw data using the Burrows–Wheeler Aligner software sorted and merged the data using the Picard tools software and identified the nucleotide variants (SNV) and insertions or deletions (indel) using GATK The GRCh37 version of the human genome was taken as reference (A,B) Cartoon representations illustrate the protein structures of both CACNA1A wild-type (wt) and the R2467P mutant The structures are color-coded by secondary elements: white represents loops On the left (blue arrow) is the wt structure On the right (red arrow) is the R2467P mutant characterized by the non-polar residue proline (C,D) Surface representations depict the protein structures of both CACNA1A wild-type (wt) and the R2467P mutant The structures are color-coded based on electrostatic values: red represents negative values (−10 min) and blue signifies positive values (10 max) On the left (within the yellow oval) is the wt structure On the right (within the green oval) is the R2467P mutant Note the discernible modification in the electrostatic surface of this Intrinsically Disordered Region (IDR) caused by the mutation (E) STRING network analysis of CACNA1A reveals a comprehensive interaction network involving proteins associated with its interaction The connections are highlighted by co-expression (black) and experimentally determined interactions (pink) Based on the criteria outlined in the joint consensus of the ACMG (American College of Medical Genetics) and AMP (American Association of Molecular Pathology) for classifying pathogenic variants we propose reclassifying this variant as a pathogenic Variant It aligns with characteristics demonstrating supporting pathogenicity (PS1) as CACNA1A is associated with autosomal dominant Developmental and epileptic encephalopathy (OMIM: 617106) familial hemiplegic with progressive cerebellar ataxia (OMIM: 141500) Spinocerebellar ataxia (OMIM: 183086) and Lennox–Gastaut syndrome (OMIM: 615369); (PS2) as the mother has one of the variants and the father has the other variant; its low frequency in control databases (PS4) and moderate evidence of pathogenicity (PM4) based on the conservation of the nucleotide Common neurological disorders of this age like generalized idiopathic seizures including juvenile myoclonic epilepsy and tonic–clonic seizures on awakening lack of cognitive and psychiatric alterations This comprehensive exploration provides a foundation for understanding the unique neurologic and psychiatric features observed in our adolescent patients These healthy females exhibited typical motor and neurological development until age 15 displaying progressive symptoms from seizures to motor and cognitive alterations Patient B presented additional psychiatric symptoms we identified 27 nonsense variants of the AARS gene: 16 classified as pathogenic nine as variants of uncertain significance These nonsense variants have been associated with conditions such as Charcot–Marie–Tooth disease type 2 Developmental and epileptic encephalopathy type 29 axonal type 2N Charcot–Marie–Tooth disease The variant most like ours was categorized as pathogenic for Charcot–Marie–Tooth disease type 2 resulting in a p.Y690* mutation (NC_000016.10: 70258139: A > C) Both of our patients present with a mutation in the AARS gene but they are the first of their mother’s family side with symptoms suggesting incomplete penetrance and an autosomal dominant inheritance both patients present with a mutation in the CACNA1A gene The latter presented with migraines during his teenage years and four other family members of their father’s family side have reported seizures Comprehensive whole exome sequencing was performed thoroughly examining all genes associated with the clinical symptoms and additional genes as specified previously This led us to identify AARS and CACNA1A as the only genes likely to be implicated in the etiology of the condition We speculate that having these two mutations could explain the fast progression of symptoms and deterioration emphasizing the significance of comprehensive family history assessment contributes to a more accurate understanding of genetic conditions and facilitates proactive health management Our study unravels a complex interplay of genetic factors contributing to a novel phenotype in two adolescent patients with a dual mutation in the AARS and CACNA1A genes The distinct progression of symptoms from seizures to motor and cognitive alterations including psychiatric symptoms in Patient B challenges the conventional understanding of AARS-related phenotypes The CACNA1A mutation further adds to the complexity showcasing a broad phenotypic spectrum with significant incomplete penetrance The familial inheritance of these mutations correlates with an accelerated symptom progression emphasizing their potential role in the clinical manifestation We underscore the essential role of genetic testing highlighting the need for international collaborations to improve healthcare accessibility and emphasizes the significance of detailed family history documentation for a comprehensive and collaborative approach to genetic research and healthcare ensuring universal access and proactive management for individuals and families with complex genetic conditions The datasets presented in this article are not readily available because of ethical and privacy restrictions Requests to access the datasets should be directed to the corresponding author The studies involving humans were approved by CEISH Universidad San Francisco de Quito The studies were conducted in accordance with the local legislation and institutional requirements Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article The author(s) declare financial support was received for the research This work was funded by the Academic Articles Publication Fund of Universidad San Francisco de Quito USFQ The authors are indebted to the patients and the parents for their willingness to participate in this study The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2024.1376643/full#supplementary-material Comparison of cognitive impairment between patients having epilepsy and psychogenic nonepileptic seizures 2. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Vanessa I. Romero, dnJvbWVyb0B1c2ZxLmVkdS5lYw== Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish Programme Director for the MSc Quality and Safety in Healthcare Management delivered a keynote presentation at the HMI conference titled “The Irish Safety Culture and After Action Review Experience (iCAARE) study – implications for healthcare managers.” McCarthy is co-investigator of the iCAARE study which examined the implementation and effect of AARs over a year at one hospital site in Ireland McCarthy explained that After Action Reviews (AARs) originated in the US military as a method for learning from training missions This practice has since been adopted by various industries AARs involve a group reflecting on four key questions: the Health Service Executive (HSE) in Ireland has integrated AARs into its National Incident Management Framework The RCSI Graduate School of Healthcare Management trained approximately 500 healthcare staff as AAR facilitators through in-person simulation-based training between 2018 and 2001 Recognising the need for innovation in learning from patient safety events AARs were advanced in the Irish Health System before a strong evidence base was established comprising researchers and knowledge users Drawing on an iCAARE publication in Safety Science McCarthy’s presentation focused on enablers and barriers to AARs and identification of behaviour change techniques to support implementation alongside potential implications for healthcare managers She shared key enablers to AAR implementation Key barriers to AAR implementation included: McCarthy suggested that addressing reinforcement and environmental constraints could help mitigate potential barriers related to emotions and social roles She also noted strong reinforcement of AARs during the early stages of adoption is crucial To enhance enablers and overcome barriers, McCarthy emphasized the use of a portable recorded resource of simulated AAR. Developed by the iCAARE research team and available in BMJ Open Quality four open access videos have been produced These open access videos are being used widely in the HSE and other countries to support AAR awareness and training McCarthy recommended the videos to the audience of healthcare managers and suggested healthcare managers prioritise AAR awareness and training for staff and address any practical and emotional barriers to AARs among staff she recommended to the audience to keep abreast of iCAARE team updates in the coming months which will feature additional study findings and strategies to support AAR This implementation science research study was funded by a HRB Applied Partnership Award with co-funding from the HSE National Quality and Patient Safety Directorate Dr Natasha Rafter is the iCAARE Principal Investigator and Ms Lorraine Schwanberg the Lead Knowledge User.  The HMI is the professional body for healthcare managers across all sectors of the health services in Ireland Its overall aim is the development of standards of management competence and practice educate and involve members and stakeholders in professional development and networking activities © Health Management Institute of Ireland (HMI) 2025 | Digital content by The Learning Rooms, Dublin Our Executive Team and Board of Directors are highly experienced members of the Railroad Industry and bring perspectives from several Class I railroads as well as other transportation and service related fields he turned a railroad service company with a single backhoe into one of the nation's leading railroad service providers Our vision is to be the BEST service provider to the railroad and related industries Our over 50 years in the railroad industry equips us with the experience and knowledge to consistently meet customers' needs We are on call 24/7 to make sure you get rapid responses to emergencies Our strategically located field offices enable us to get on site quickly We excel in developing communication solutions From engineering highway crossing warning systems to wayside signals we can provide turnkey services at any level These crews and their equipment are formed from the combined resources of multiple companies to provide a concentrated high-quality and cost-effective inventory management and point-of-use delivery Our 19 short line railroads operate in 11 states serving customers with a wide variety of commodities We have 30+ years of experience providing safe and reliable transportation We provide railroad operational support to a wide variety of industrial facilities that ship via rail Our services can be greatly customized to suit our customers’ needs We stand ready to provide secure material warehousing and transloading services to customers in locations with or without railroad access With year-round excursions in Kentucky’s beautiful countryside this passenger dining experience offers the perfect pairing of delicious food and delightful scenery Keep up to date with the latest activity from R Corman and follow us on Facebook and Twitter Find out how to bid on funded projects for R To request wire line or pipe line installation 859-881-7521 1-800-772-9091 info@rjcorman.com 42 railroaders participated in an American Association of Railroad Superintendents (AARS) training hosted by our company It was two days full of highly technical training in Train Accident Prevention and Investigation the American Association of Railroad Superintendents has served as networking and development group for railroad operations leadership and management of Class I and passenger railroads in North America.  Railroaders from different parts of the country ranging from Class I and regionals to short lines and transit railroads The sessions were led by experienced railroaders Bruce Rose and Jimmy Grupposo and included topics such as recording track geometry The hands-on training portion took place at the R Corman Central Kentucky Lines' Lexington Yard It included an engineering section with track notes & turnout inspection training and a mechanical portion with detailed instructions on car inspection For more information about the AARS, please visit their website: American Association of Railroad Superintendents Volume 13 - 2022 | https://doi.org/10.3389/fphys.2022.1029218 This article is part of the Research TopicNoncanonical Functions of Aminoacyl-tRNA SynthetasesView all 5 articles The Aminoacyl-tRNA Synthetases (aaRSs) are an evolutionarily ancient family of enzymes that catalyze the esterification reaction linking a transfer RNA (tRNA) with its cognate amino acid matching the anticodon triplet of the tRNA Proper functioning of the aaRSs to create aminoacylated (or “charged”) tRNAs is required for efficient and accurate protein synthesis Beyond their basic canonical function in protein biosynthesis aaRSs have a surprisingly diverse array of non-canonical functions that are actively being defined The human genome contains 37 genes that encode unique aaRS proteins 56 human genetic diseases caused by damaging variants in aaRS genes have been described: 46 are autosomal recessive biallelic disorders and 10 are autosomal dominant monoallelic disorders Our appreciation of human diseases caused by damaging genetic variants in the aaRSs has been greatly accelerated by the advent of next-generation sequencing with 89% of these gene discoveries made since 2010 In addition to these genetic disorders of the aaRSs anti-synthetase syndrome (ASSD) is a rare autoimmune inflammatory myopathy that involves the production of autoantibodies that disrupt aaRS proteins This review provides an overview of the basic biology of aaRS proteins and describes the rapidly growing list of human diseases known to be caused by genetic variants or autoimmune targeting that affect both the canonical and non-canonical functions of these essential proteins emerging during the time of the last universal common ancestor (LUCA) and are distributed across all branches of life Given their central role in human biology, it is unsurprising that genetic variants that disrupt aaRS protein structure and function cause disease. Damaging variants in aaRSs have now been linked to over 50 human diseases (Figure 1A) Notably 2/3 of these newly recognized diseases have only been described in the past decade since next-generation sequencing technologies have become more widely available This review will provide an overview of the basic biology of aaRS proteins and will describe the rapidly growing list of human diseases known to be caused by variants that affect both the canonical and non-canonical functions of these essential proteins We anticipate this review will be of value to clinicians who care for patients with diseases related to aaRS function and scientists interested in the links between the aaRSs and disease (A) The timeline of discovery of biallelic and monoallelic human diseases caused by damaging aaRS variants since 2000 (B) Overview of the esterification reaction that charges a tRNA molecule with its cognate amino acid This charged tRNA then travels to a translating ribosome where it recognizes a codon and adds its amino acid to the growing polypeptide chain (C) General characterization of symptoms associated with diseases caused by monoallelic and biallelic pathogenic aaRS variants Diseases caused by monoallelic variants are typically late-onset The synthesis of functional proteins relies on the accurate transfer of genetic information from DNA DNA is first transcribed to mRNA using the complementarity of nucleotide bases The mRNA is then translated into a protein by the ribosome The ribosome reads the mRNA in groups of triplet codons with each codon corresponding to one amino acid elongation factors bring a tRNA containing the three bases complementary to a codon (anticodon) and charged with the correct amino acid The amino acid delivered by the tRNA is then added to the growing polypeptide chain following the order of codons specified by the mRNA This elongating polypeptide eventually becomes a functional protein within the cell all living organisms contain genes for the 20 aaRSs The degeneracy of the genetic code means that there are more codons than amino acids the aaRS for an amino acid can recognize several tRNAs cognate to that amino acid Eukaryotes contain genes for cytoplasmic and mitochondrial aaRSs (and in plants All of these proteins are nuclear encoded and synthesized in the cytoplasm with the organellar aaRSs being imported to their final destinations following translation Our understanding of these non-canonical functions of aaRSs is growing rapidly. As we try to understand how pathogenic genetic changes in the aaRS genes cause human disease, it is essential that we look beyond the canonical aminoacylation role of aaRSs and consider how alterations in non-canonical functions may also contribute to pathophysiology (Guo et al., 2010b) The naming convention for genes encoding aaRSs is as follows: 1) gene names begin with the one-letter symbol for the amino acid the aaRS recognizes (e.g. A for alanine; Y for tyrosine); 2) this is followed by ARS1 or ARS2 depending on whether the aaRS is located in the cytoplasm or mitochondria which charges a tRNA molecule with leucine in the mitochondria of the cell While the single-letter amino acid code is used for aaRS gene names the 3-letter amino acid code is generally used as a prefix to refer to the protein product In total, human cells contain 37 genes that encode unique aaRS proteins. Of these, 18 encode cytoplasmic aaRSs (2 of these genes encode cytoplasmic PheRS), 17 encode mitochondrial synthetases, and two genes encode proteins that will exist in both locations (Wei et al., 2019) TABLE 1. Complete list of each aaRS-encoding gene and every human disease in the Online Mendelian Inheritance in Man resource (OMIM - https://www.omim.org) caused by damaging monoallelic and biallelic variants in that gene To date, 10 monoallelic diseases arising from autosomal dominant variants in seven aaRS genes (NARS1, HARS1, GARS1, AARS1, MARS1, WARS1, YARS1) have been identified (see Table 1) all of these monoallelic conditions occur in cytoplasmic AARS-encoding genes CMT is divided into various subtypes, with demyelinating Type 1 CMT (CMT1) and axonal Type 2 CMT (CMT2) containing the majority of cases. Demyelinating Type 1 CMT occurs from breakdown of the myelin sheath of nerves, while Type 2 axonal CMT occurs from direct damage to the axons of nerves (Harding and Thomas, 1980; Bird, 1993; Teunissen et al., 2003) Intermediate CMT has features of both Type 1 and Type 2 While over 90 genes have been linked to the pathogenesis of CMT, aaRS-encoding genes constitute the largest gene family connected with this disorder (Bansagi et al., 2015; Blocquel et al., 2019) variants in seven cytoplasmic aaRS genes have been established to cause CMT (YARS1 All of these genes except YARS1 and KARS1 are associated with monoallelic axonal CMT (CMT2) KARS1 is an outlier in that it causes autosomal recessive CMT and specifically the intermediate B subtype In recent studies, a complementary pair of papers by Zuko et al. and Spaulding et al. expanded our understanding of disease mechanisms in CMT (Mellado and Willis, 2021; Spaulding et al., 2021; Zuko et al., 2021) The investigators found that a disease causing GlyRS variant bound tRNAGly but failed to release it This sequestration likely reduced the cellular tRNAGly pool leading to insufficient tRNAGly supply to the ribosome they observed ribosome stalling at glycine codons and chronic activation of the damaging integrated stress response (ISR) in affected motor neurons through the sensor kinase GCN2 these complementary studies identified two strategies with potential therapeutic benefit: 1) overexpression of tRNAGly to rescue protein synthesis avoiding ISR activation and the ensuing peripheral neuropathy; or 2) inhibiting GCN2 to avoid activation of the neurotoxic ISR the mechanism(s) linking aaRS variants to human CMT remains an area of intense investigation with the ultimate goal of developing treatments that will prevent neurodegeneration in patients born with aaRS variants that cause CMT While CMT is the most common monoallelic condition associated with aaRS variants several other related neurological conditions are caused by damaging aaRS variants It is helpful to appreciate that borders between these disease definitions are rather ‘porous’ and that these additional monoallelic aaRS-related conditions share features with CMT and with each other Distal hereditary motor neuronopathy (dHMN) is a pure motor neuropathy characterized by progressive distal muscle weakness and muscular atrophy without sensory impairment. Pathogenic variants in both WARS1 and GARS1 have been associated with dHMN (Antonellis et al., 2003; Tsai et al., 2017) Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (designated NEDMILEG) is reported to be caused by de novo heterozygous variants in the NARS1 gene (Manole et al., 2020) bi-allelic variants in NARS1 also cause a similar neurodevelopmental disease The mechanism of disease for the de novo heterozygous variants was suggested to be toxic gain-of-function while the bi-allelic recessive variants were thought to cause disease through partial loss-of-function James type of infantile spinal muscular atrophy (SMAJI) is a severe neuromuscular disorder with symptoms beginning in the first weeks or months of life. Several unrelated children with SMAJI have been found to have de novo heterozygous variants in GARS1 (James et al., 2006; Eskuri et al., 2012; Forrester et al., 2020; Markovitz et al., 2020) Biallelic diseases arising from the disruption of both alleles of genes encoding the aaRSs cause severe early-onset disorders affecting multiple organ systems Biallelic disease can be caused by homozygous or compound heterozygous variants This amino acid supplementation was well-tolerated and safe and showed encouraging results in terms of improvements in growth and ability to cope with intercurrent infections It is anticipated that this result will encourage more trials in additional patients to more formally assess the safety and efficacy of this treatment approach which targets the underlying aminoacylation defect in patients with autosomal recessive aaRS deficiencies Biallelic aaRS diseases are multi-system disorders with significant cross-over between phenotypes. It is likely that more clarity will emerge around the clinical phenotypes as more patients and more genetic diagnoses are described. Indeed, Fuchs et al. emphasized the importance of deep phenotyping of patients with aaRS-related diseases and reporting all clinical features, so the full extent of the phenotypes can be appreciated (Fuchs et al., 2019) For simplicity we have divided this section into biallelic disorders affecting mitochondrial or cytoplasmic aaRSs There is clear cross-over between the manifestations of the disorders caused by biallelic mitochondrial and cytosolic aaRS variants which will only be resolved through the sequencing and careful phenotyping of more affected individuals The recent rapid advances in defining the role of aaRSs in human disease opens many avenues for life changing improvements in diagnosis and targeted treatment The ability to provide a complete genetic diagnosis for individuals with monoallelic or biallelic aaRS diseases is transformative in many ways—new treatments can be explored based on the genetic findings (i.e. new potential medical issues or risks can be anticipated and 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use *Correspondence: Alexandra K. Turvey, YXRhYjIwMjBAbXltYWlsLnBvbW9uYS5lZHU= The American Acne and Rosacea Society (AARS) has published a guideline update on the management of rosacea, with new recommendations focused on emerging rosacea therapeutic agents and formulations The update was published in a recent edition of the Journal of Clinical and Aesthetic Dermatology Summary of Rosacea Guidance: Updates on New Agents published guidelines for rosacea typically recommend proper skin care and avoidance of triggers as the cornerstones of prevention But new evidence supporting novel therapeutic agents has emerged since previous guidance statements Below is a summary of the new AARS recommendations regarding new and established agents based on rosacea presentation Persistent Central Facial Erythema Without Papulopustular Lesions Patients with rosacea presenting with persistent central facial erythema without papulopustular lesions may do well with a topical alpha-agonist therapy Studies cited in the guideline suggest topical brimonidine and oxymetazoline improve diffuse facial erythema and produce a better facial appearance compared with devices alone the AARS recommends intense pulsed light (IPL) potassium titanyl phosphate (KTP) crystal laser or pulsed dye laser as adjunct or alternative therapies for persistent central facial erythema without papulopustular lesions Comments made by the guideline committee indicate the need for more data on the optimal use of device therapies in combination with alpha-agonist therapies in these patients Diffuse Central Facial Erythema With Papulopustular Lesions For cases of diffuse central facial erythema with papulopustular lesions the AARS recommends several topical and oral therapies The guideline cites research that demonstrates the successful use of 1% oxymetazoline cream for reducing persistent facial erythema and perilesional erythema in combination with topical metronidazole In patients with severe papulopustular rosacea subantibiotic dose doxycycline with azelaic acid may the preferred initial oral treatment due to the absence of bacterial selection pressure the guideline update recommends oral azithromycin as an alternative approach if oral tetracycline is deemed ineffective or is poorly tolerated by the patient Clinicians should counsel patients on the potential cardiac risks for tetracycline especially if they have cardiovascular risk factors clinicians may wish to start oral isotretinoin and then transition to intermittent therapy after initial control of the disease Additional alternative topical therapies mentioned in the guideline include sulfacetamide-sulfur, calcineurin inhibitors, retinoids, and permethrin. The guideline cautions that limited data are available on these agents. Other options that may be useful for erythema include IPL, KTP, and pulsed dye laser, but the data on their efficacy for papulopustular lesions is limited In cases of acute or subacute intermittent vasodilation the AARS emphasize the importance of prevention by avoiding known triggers such as sun exposure There are currently limited data on the use of topical therapies to treat flushing the AARS recommends the use of low-dose oral agents that feature vasoconstrictive properties The guideline update cites research suggesting intradermal botulinum toxin could be helpful for flushing but limited data preclude a consensus-based recommendation for its use the AARS guideline update points to data from small preliminary studies supporting the efficacy of niacinamide and parthenolide-free extracts of feverfew for improving facial redness and flushing in rosacea Evidence-based treatment for granulomatous rosacea The evidence supporting these treatments is from small studies and case reports there is no standard treatment for granulomatous rosacea Recent evidence supports the use of carbon dioxide laser erbium-doped yttrium aluminum garnet (YAG) laser and dermabrasion as potential treatment options for phymatous rosacea Selection of treatment depends on the stage of disease development The AARS guideline suggests oral isotretinoin may improve early soft phymatous changes caused by sebaceous hyperplasia The AARS notes in the guideline that there is little data to dictate the optimal use of combination strategies for rosacea the guideline states that the current evidence suggests that it “appears that rationally selected medical therapies can be utilized concurrently” in patients with rosacea Disclosure: Several guideline authors declared affiliations with the pharmaceutical industry Please see the original reference for a full list of authors’ disclosures Del Rosso JQ, Tanghetti E, Webster G, Stein Gold L, Thiboutot D, Gallo RL. Update on the management of rosacea from the American Acne & Rosacea Society (AARS). J Clin Aesthet Dermatol Brandon May is a freelance medical writer and owner of May Medical Communications He holds a BS in Nutrition and Dietetics from the University of Houston he has written over 700 medical news articles across several different therapeutic areas Brandon also creates content for continuing medical education providers and pharmaceutical and medical device companies across the globe a trusted source of medical news and feature content for healthcare providers offers clinicians insight into the latest research to inform clinical practice and improve patient outcomes Copyright © 2025 Haymarket Media, Inc. All Rights Reserved. This material may not be published, broadcast, rewritten or redistributed in any form without prior authorization. Your use of this website constitutes acceptance of Haymarket Media’s Privacy Policy and Terms & Conditions. 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Register for free and gain unlimited access to: Please login or register first to view this content. the clock is ticking on how long they can survive This mother polar bear and her two cubs are headed down to the sea ice in the Svalbard archipelago guides Timo Virma Virta Santucci and Teemu Tissari led a group of visitors out onto the sea ice They had just crossed the island of Spitsbergen in the Svalbard archipelago located about halfway between Norway and the North Pole when they spotted a mother polar bear and her two cubs because they need the sea ice to hunt seals — their primary prey They also need it to walk to their denning areas But animals don’t always respond predictably to shifting living conditions and the polar bears of Svalbard have been resilient — at least for now this is a good hunting ground,” Tissari said studies the Barents Sea polar bear population made up of about 3,000 bears around Svalbard and Russia About 10% of them stay mostly on the land on and near Svalbard Aars said the sea ice in this area is declining more than twice as fast as anywhere else in the Arctic But the polar bears here — unexpectedly — are thriving “One explanation is that they were hunted quite extensively until they were protected in 1973,” Aars said “So … they are still in sort of a recovery phase.” The other reason lies within the bears themselves “Polar bears are what you call ‘plastic,’” Aars said “They are already designed in a way that makes it possible for them to switch the way they live.” The polar bears that live on Svalbard appear to be hunting more reindeer and taking more birds’ eggs Mother bears are swimming farther to get to their denning areas you use only a fraction of the energy that you would use if you swim the same 100 kilometers in cold water,” Aars explained And while eating reindeer may be a good survival technique which provide thick blubber that can sustain a polar bear for months While these polar bears have proven to be resilient as the sea ice continues to melt scientists do not believe they’ll be able to keep it up I think polar bears would have expanded into areas where you don’t have sea ice already,” Aars said history may be the best predictor of the future “If we go back about 10- or 11,000 years ago Now he’s a professor at the University of Alberta and works mostly with polar bears in Canada If these creatures were capable of adapting to land “We would see them in southern Alaska along the panhandle,” he said Tissari is used to seeing the earth — and the ice — beneath him change “It feels like we’re witnessing something very dramatic here,” Tissari said “This place will not be the same 20 years from now.” Santucci used to work as a guide in Finland and he traveled north to work for Svalbard Adventures “We’re going toward something that we’re not controlling,” he said And we kind of know that within the next 50 years So then,you feel that you’re doing something wrong.” That April polar bear sighting was Santucci’s first of the season He knew the visitors who experienced it had glimpsed something special It remains unclear exactly how Svalbard will change over the coming decades but it will likely lose its 300 land-loving polar bears “The fact that polar bears in Svalbard that are local never seem to move might indicate that that part of the population that is in Svalbard will just die off if sea ice disappeared for the whole year,” Aars said That doesn’t mean polar bears will disappear completely “I’m optimistic that in the very high reaches of the Arctic we’ll be able to keep the bears in those areas,” Derocher said the sea ice in the highest Arctic is too thick for polar bears “It looks like there still will be enough sea ice for them to persist,” Derocher said so that we can have those bears there in 50 or 100 years from now.” the harder it will be to catch a glimpse of them For those hoping to experience the magic of seeing a polar bear for themselves delivered to your inbox every weekday morning Thanks to our sponsor PRX is a 501(c)(3) organization recognized by the IRS: #263347402 Structural Biology is the study of the 3D arrangements of atoms in biological molecules It is an immensely rich source of information that has continually transformed how we think of ourselves Knowing a structure adds a new level of reality to an entire range of mechanistic models The double helical structure of DNA likely brought the most fundamental overhaul of our perspective It showed that units we had called “genes” have a structure that makes the idea of a “heritable blueprint” unmistakably self-explanatory Dennis Noble argues in a review of Phillip Ball’s new book (2) Understanding that the reality is indeed much more interesting is crucial because of how it informs policy One of the ways to see his argument is to recognize how much is missing from the blueprint metaphor The essence of the metaphor is that blueprints must be read out Reading genes out has two implications that tend to be ignored it implies a reflexive symbolic translation from one chemical language to another AARS distinguish between 20 kinds of amino acids and 61 kinds of transfer (t)RNAs they form a chemical bond between them (Fig (3) That bond cements the translation of the code by connecting amino acids to RNAs containing the right symbols (called “codons”) The search for the origin of translation will succeed when we can describe the earliest AARS*tRNA “cognate pairs” and the rules by which the AARS recognized their two kinds of substrate translation creates protein products that form the core networks that power the cell often reflexive interactions between the elements of those networks and regulatory proteins – amplify the functions of their genes by an immense factor Our quest for how Nature assembled the first AARS•tRNA cognate pairs has tried to adhere to the tenet that two things must have been true of ancestral AARS Experimental Biochemistry is the only means we have to assess functionality Phylogenetics is the only record we have of what sequences might have survived a nearly random ancestry The survival of those sequences and their ancestral functionality are clearly interdependent Structural Biology played a key role in bringing us as far as we’ve come My four previous segments (3,4,7,8) tell much of that story so far 1 to summarize where I think the field has come Aligning the 3D atomic coordinates of all members of each AARS Class revealed that both superpositions show a sharp contrast between a common core those highly variable surface loops are inserted into the same places within the cores the core-loop junctions can be replaced by a single peptide bond These aspects of AARS molecular anatomy pointed us directly at the structural cores It was conceptually straightforward to construct genes for the cores themselves and only moderately difficult to purify them and show that they retained most of the catalytic proficiency of their full-length (putative) descendants That path has thus far given us four AARS urzymes that exhibit more or less complementary amino acid specificities we also discovered ways to tease out details of how ancestral AARS recognized their cognate RNA substrates by an operational code (4) We related those specificities and the recognition of Class I and II amino acid substrates to projections of base- pairing between ancestral genes into the proteome They only set the stage for the main tasks that remain to be taken on The ultimate puzzle is how Nature built a set of protein decoders that could enforce the coding rules by which they That task is outlined in the details in (Fig 1) It entails genes written with an alphabet with as few as two distinct kinds of amino acids The translated products of those genes had to fold into 3D structures whose catalytic apparatus and RNA substrate recognition could then impose the coding rules required to read their own gene sequences A critical missing piece is to strengthen the computer algorithms used to deduce ancestral sequences (10,11) We analyze amino acid sequence alignments from many contemporary genes for positions where they differ and then estimate from the distributions of different side chains at those positions which amino acids the likely common ancestor used at that position The biochemical tools we have developed should then provide the experimental platform to characterize those ancestral sequences This article first appeared in Open Access Government April 2024 To view the article click here License: CC BY-NC-ND 4.0 This work is licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International. 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Click here to login Please enable JS and disable any ad blocker Metrics details The authors carried out a comprehensive search for alternative splice variants of 37 human aaRSs in brain tissues and in leukocytes using gene-specific multiplex PCR of exon–exon junctions They discovered hundreds of novel splice variants and found that 60 of the 70 identified internal in-frame splice variants abrogated the highly conserved catalytic domain but retained at least one of the later-gained domains These variants are therefore catalytic nulls in regard to the canonical function of aaRSs but they may have other biological functions the observed loss of specific exons could potentially lead to extensive structural changes and thus create new protein interactions Human tRNA synthetase catalytic nulls with diverse functions Download references Reprints and permissions Download citation a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science By Penny Sarchet (Image: © Samuel Blanc / www.sblanc.com) They’re two of the world’s most loved animals – but there’s little love between them Jon Aars of the Norwegian Polar Institute and his colleagues have made the first ever observations of polar bears eating white-beaked dolphins that had ventured too far north – in fact they saw this happen several times last year The first incident was in late April 2014. Collecting data in Svalbard, Norway Aars’s team stumbled across a bear with two dead white-beaked dolphins a species no one had ever seen the bears preying upon before [using] a similar technique as killing seals,” says Aars He thinks it probably caught the two dolphins when they found a small hole and surfaced for air had already eaten most of the first dolphin but couldn’t finish all of its catch in one sitting storing a second dolphin – still largely intact – under the snow for a later snack (Image: Jon Aars/Norwegian Polar Institute) Hiding leftover food is a rare behaviour in polar bears “We think he caught the second dolphin because he could and then had extra food later,” says Aars the team came across at least five other polar bears feeding on dead dolphins in the same area “We were surprised as dolphins have not been reported in that area before,” says Aars The explanation could be that the Svalbard waters were unusually warm at the time and that a pod of dolphins had become trapped there when strong northerly winds had pushed them out of open water and in among the ice Ian Stirling of the University of Alberta in Canada is not surprised that the bears decided to feast on dolphin meat: polar bears are known to be opportunistic predators and have been recorded eating many different animals “They will eat any marine mammal given a chance,” he says “The bigger surprise was that the dolphins were entrapped before they could migrate south for the winter.” Stirling believes the sight of polar bears tucking into weird meals could become more common Polar bears are “willing to take and use anything possible when available” Journal reference: Polar Research, DOI: 10.3402/polar.v34.26612 IFLR is part of Legal Benchmarking Limited Copyright © Legal Benchmarking Limited and its affiliated companies 2025 Accessibility | Terms of Use | Privacy Policy | Modern Slavery Statement The content you are trying to view is exclusive to our subscribers You have reached the limit for gifting for this month Thank you for completing the form, here is your download: "+jQuery("body").attr("docName")+" Thank you for completing the form, here is the link to your on-demand webinar: On-Demand Webinar Link Do you remember the fire when everything went perfect The one where you wouldn’t do a single thing differently if you had the chance to do it over again Structural firefighting operations and various other types of complex and dynamic emergency incidents are rarely completed in a manner that eliminates any room for improvement There really are no “perfect fires.” That’s not a bad thing and it’s certainly not an indictment on our industry’s skill level or dedication It simply means that getting everything exactly right in the exceedingly dynamic environment in which we operate is just a really tough task One of the most productive opportunities we have as a fire service is to remain humble and self-reflective following significant incidents We should certainly celebrate the positive outcomes and acknowledge the smart choices that were made in a high-stress But we’re doing no one any good if we gloss over or ignore the minor (sometimes even major) tactical operations that could have been handled in a safer or more efficient manner Departments that regularly conduct after-action reviews (AAR) are well-positioned to streamline their performance on emergency incidents and increase their margin of operational safety The format in which these reviews are performed varies widely from department to department some organizations don’t engage in the AAR process at all FireRescue1 surveyed thousands of firefighters from across the country for the inaugural “What Firefighters Want” survey and the results surrounding AAR were surprising One-third of respondents noted that AAR are conducted in their organizations rarely or never And while it’s possible that some of the survey respondents may not perform reviews often due to a low volume of incidents the more likely scenario is that many departments simply don’t buy in to the critical nature of the AAR concept This theory is supported by the many survey respondents who called for more AARs Here’s a snapshot of some of the 100+ AAR-focused responses: If your department needs help focusing on AARs An after-action review can encompass any type of post-incident reflection that objectively evaluates performance and results in a plan for improvement Even complex training events can sometimes elicit an AAR although most revolve around incident mitigation An effective way to get the AAR concept off the ground is to look around and see what other departments are doing Most departments that regularly conduct AAR will have some type of policy that prescribes what level of detail and formality is required for various categories of incidents such as automatic fire alarm activations or BLS medical responses etc.) or ALS medical incident may simply elicit some conversation amongst the crew on the way back from the incident about what went smoothly and if any notable safety concerns were observed by any crewmembers A working structure fire may trigger a post-incident “tailboard chat” among the incident commander and the company officers before everyone begins to pick up to leave these quick talks can reinforce expectations make note of the efficiency of various tactical operations and provide an opportunity for the less-experienced officers to ask questions and get feedback civilian fire fatalities or a mayday event should prompt a formal AAR process a committee may be formed to investigate the incident operations and provide a formal report with recommendations In the event of a catastrophic firefighter injury or a confirmed line-of-duty death (LODD) ICs and senior staff members need to remain cognizant of the need to preserve the scene for comprehensive investigative procedures and various state and federal agencies are all likely to have a need to assess the scene in the hours and days following such an event Some fire departments have produced extraordinarily detailed and comprehensive internal reports following a serious injury or LODD in their organization A best practice for these expansive investigative documents is to establish a cross-sectional committee that involves senior internal leadership external non-biased subject-matter experts and representatives from other interest groups such as volunteer associations or dispatch The issue of photography and/or videography by departmental personnel on an active scene has been a frequently debated topic in the fire service record-keeping and logistics will all be determining factors in whether a department allows such activity there is no denying that helmet camera or dash camera footage from an active fireground is invaluable for training and AAR purposes particularly when paired with incident audio recordings can provide a vivid picture of tactical operations that serves as context for myriad uses within the department and community Some departments have taken an aggressive approach to “telling their story” on social media and other public forums to notable success and positive feedback that cameras capture both the good and the bad and departments must be cognizant of laws on record keeping and retention informal discussions all the way to comprehensive reports produced by large committees the key is to establish a culture of self-reflection and self-improvement within the organization It may be an informal discussion amongst the crew on the way back from an incident or an afternoon spent quietly studying an investigation report for an LODD as well as vicariously learning from others is a healthy part of any organizational culture Brad French is a captain in the Dayton (Ohio) Fire Department He is a 20-year member of the fire service and holds degrees in fire science and fire administration French is a former member of the Board of Directors for the International Society of Fire Service Instructors (ISFSI) serves on the technical committees for NFPA 1700 and 1402 and is a member of the technical panel for the UL-FSRI Coordinated Fire Attack study Copyright © 2025 Lexipol. All rights reserved.Do Not Sell My Personal Information Christian Aars puts the universe into perspective with images from the James Webb Space Telescope during a presentation at Our Savior’s Lutheran Church at Norse To access content, please login or purchase a subscription to Bosque County Record-Tribune Read Bosque County Record-Tribune This is not the RTO Insider site you are looking for.Unless it is There was a problem resetting your password Sign In Register These corporate claims were filed with the B.C Information is derived from notices of civil claim Civil claims have not been tested or proven in court.  and Aars Shiddheek also known as Aars Shiddeek also known as Aar Aboobucker Shiddheek also known as Aar Subuhan Shiddheek $470,788 and $159,885 and $744 to cover loans to Access Superior Mechanical that were guaranteed by Shiddheek $428,984 and $24,975 to cover loans to the numbered companies that were guaranteed by Shiddheek Damages for breach of agreement and breach of the duty of confidence after the defendant downloaded confidential information on the plaintiff’s contractors staff and customers before launching a competing business $132,000 to repay a loan from the shareholder plaintiffs to the defendant continue with an agreement with the plaintiff to honour its one-half interest in a property the defendant was also a tenant of Metrics details The new insights arose from analysis of a mutant mouse strain which earned the name sticky (Sti) because of its dishevelled fur Sti mice suffer from slow progressive degeneration of cerebellar Purkinje cells leading to motor defects reminiscent of many neurodegenerative conditions Ackerman and colleagues therefore set out to determine the genetic defect underlying this neurodegeneration The authors pinned down the mutation to the alanyl-tRNA synthetase (Aars) gene the amino acid alanine to appropriate tRNA (tRNAAla) molecules and is crucial for the translation of mRNA transcripts into accurate peptide sequences The mutation affects the editing domain of AARS which deacylates tRNAAlamolecules that are mistakenly bound to similarly sized but inappropriate amino acids the mutation reduced the ability of the enzyme to deacylate serine–tRNAAla molecules whereas the capacity to recognize alanine and catalyse appropriate aminoacylation reactions was unaffected Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration Download references Reprints and permissions Download citation scientists have noticed something disturbing: polar bears are catching and eating white-beaked dolphins that have ventured too far north While polar bears eating cute aquatic mammals is nothing new the fact that the two species have crossed path raises some red flags The first observation of this encounter happened in April 2014. Jon Aars of the Norwegian Polar Institute was collecting data in Svalbard Norway when he stumbled upon a bear with two dolphin carcasses Aars and his colleagues had never seen this sort of encounter before "We were surprised as dolphins have not been reported in that area before," Aars told NewScientist The polar bear likely caught these rogue dolphins similar to how it catches seals: Dolphins periodically surface in holes in the ice in order to breathe which means a patient bear could sit and wait for the right moment to snatch its prey the frugal bear stores the rest of its kill in the ice for later Since this first sighting, at least five more bears have added dolphin to their menus This disturbing trend is likely the result of global warming Scientists believe the dolphins ventured north earlier than usual due to unseasonably warm weather and were then blown off-course and stuck in polar bear country As a group of scientists explained in Polar Research "We suggest they were trapped in the ice after strong northerly winds the days before and possibly killed when forced to surface for air at a small opening in the ice." © 2025 Minute Media - All Rights Reserved Mental Floss may receive a commission for purchases made through these links.",{"type":"6a","value":"fr"},"AR_1",{"type":"6a","value":"ft"},"This article contains affiliate links to products selected by our editors as well as products provided to Mental Floss for review purposes d) {\n h = h[d] = h[d] || {\n q: [],\n onReady: function(c){ h.q.push(c) },\n };\n d = o.createElement(u);\n d.async = 1;\n d.src = n;\n n = o.getElementsByTagName(u)[0];\n n.parentNode.insertBefore(d \"https://www.datadoghq-browser-agent.com/us1/v5/datadog-rum.js\" Initialize Datadog RUM and then measure TTFB/FCP\n window.DD_RUM.onReady(function() {\n // 3a Initialize RUM\n window.DD_RUM.init({\n applicationId: 'f3f16add-4ebf-4aad-9bb4-adb13da4d17e',\n clientToken: 'pub53fad8ec1eea29e2f92980d95072da2f',\n site: \"datadoghq.com\",\n service: \"voltax-sites-www.mentalfloss.com\",\n env: \"prod\",\n sessionSampleRate: 100,\n sessionReplaySampleRate: 0,\n trackUserInteractions: true,\n trackResources: true,\n trackLongTasks: true,\n defaultPrivacyLevel: \"mask-user-input\",\n });\n\n // 3b Measure TTFB & FCP once the page fully loads\n window.addEventListener('load' {\n ttfb: ttfb,\n fcp: fcp,\n });\n\n // Optional: log them to console for debugging\n console.log('[Datadog RUM] TTFB:' The first observation of this encounter happened in April 2014. Jon Aars of the Norwegian Polar Institute was collecting data in Svalbard "We were surprised as dolphins have not been reported in that area before," Aars told NewScientist Since this first sighting, at least five more bears have added dolphin to their menus As a group of scientists explained in Polar Research