NARS Human

Asparaginyl-TRNA Synthetase Human Recombinant
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Description

Biochemical Properties of Recombinant NARS Human

NARS Human is produced in two recombinant systems with distinct characteristics:

PropertySf9 Insect Cell Expression E. coli Expression
Molecular Mass63.8 kDa (glycosylated)65.3 kDa (non-glycosylated)
TagN-terminal 6xHisN-terminal 23-amino acid His-tag
Purity>80% (SDS-PAGE)>80% (SDS-PAGE)
Storage-20°C in 20% glycerol buffer-20°C with 10% glycerol & carrier protein
ApplicationsLaboratory research onlyLaboratory research only

Both forms retain enzymatic activity and are used to study NARS1's role in tRNA charging and protein synthesis .

Molecular Functions and Pathways

  • Core Function: Catalyzes asparagine activation via ATP to form Asn-AMP, followed by tRNA(Asn) charging .

  • Non-canonical Roles:

    • Induces chemotaxis in CCR3-expressing cells (e.g., eosinophils) through its N-terminal domain .

    • Regulates radial glial cell (RGC) proliferation during cortical brain development .

Key Pathogenic Variants and Phenotypes

  • Biallelic Mutations:

    • p.T17M (UNE-N domain): Reduces protein stability by 50% and impairs tRNA charging activity .

    • p.Arg534* (catalytic domain): Causes autosomal recessive neurodevelopmental disorders .

  • De Novo Heterozygous Mutations:

    • p.Arg322Leu and p.Gly509Ser: Linked to dominant epileptic encephalopathy .

Associated Disorders

ConditionInheritanceKey Features
Neurodevelopmental disorder with microcephaly (OMIM:619091)RecessiveImpaired RGC proliferation, global developmental delay, cortical organoid shrinkage
Neurodevelopmental disorder with epilepsy (OMIM:619092)DominantEarly-onset seizures (<1 year), gait abnormalities, demyelinating neuropathy

Functional Studies and Organoid Models

  • Patient Fibroblasts: Show 50% reduced NARS1 protein levels and impaired global protein synthesis (puromycin assay) .

  • Cortical Organoids:

    • NARS1-deficient organoids exhibit 60–70% size reduction due to RGC proliferation defects .

    • Single-cell RNA-seq reveals altered cell-cycle pathways (e.g., CCND1 downregulation) .

Therapeutic Implications

  • Enzyme Replacement: Overexpression of wild-type NARS1 partially rescues mitochondrial respiration in patient cells .

  • Targeted Therapies: Small molecules enhancing NARS1 stability or tRNA charging activity are under exploration .

Research Tools and Antibodies

  • Antibodies: Anti-NARS1 (Novus Biologicals, NBP1-31896) validated for Western blotting .

  • SNP Genotyping: Illumina Core-Exome-24 Kit used for variant analysis in clinical studies .

Product Specs

Introduction
Aminoacyl-tRNA synthetases are enzymes that attach tRNAs to their corresponding amino acids. Asparaginyl-tRNA synthetase (NARS), found in the cytoplasm, belongs to the class II family of tRNA synthetases. A key characteristic of eukaryotic asparaginyl-tRNA synthetases is the signature sequence located in their N-terminal domain.
Description
Recombinant human NARS, produced in E. coli, is a single, non-glycosylated polypeptide chain consisting of 571 amino acids (with amino acids 1 to 548 being part of the NARS sequence) and has a molecular weight of 65.3 kDa. This protein is engineered with a 23 amino acid His-tag at the N-terminus and is purified using proprietary chromatographic techniques.
Physical Appearance
A clear, colorless solution that has been sterilized by filtration.
Formulation
The NARS protein solution has a concentration of 0.25 mg/ml and is prepared in a phosphate buffered saline solution (pH 7.4) with 10% glycerol.
Stability
For short-term storage (2-4 weeks), keep the vial refrigerated at 4°C. For extended periods, freeze the solution at -20°C. Adding a carrier protein (0.1% HSA or BSA) is advisable for long-term storage. Avoid repeated freezing and thawing of the solution.
Purity
The purity level is determined to be above 80% based on SDS-PAGE analysis.
Synonyms
NARS, Asparaginyl-TRNA Synthetase, AsnRS, EC 6.1.1.22, Asparaginyl-TRNA Synthetase, Cytoplasmic, Asparagine TRNA Ligase 1, Cytoplasmic, Asparagine--TRNA Ligase, Cytoplasmic, Asparagine TRNA Ligase 1, Cytoplasmic, NARS1.
Source
E.coli.
Amino Acid Sequence
GSSHHHHHH SSGLVPRGSH MGSMVLAELY VSDREGSDAT GDGTKEKPFK TGLKALMTVG KEPFPTIYVD SQKENERWNV ISKSQLKNIK KMWHREQMKS ESREKKEAED SLRREKNLEE AKKITIKNDP SLPEPKCVKI GALEGYRGQR VKVFGWVHRL RRQGKNLMFL VLRDGTGYLQ CVLADELCQC YNGVLLSTES SVAVYGMLNL TPKGKQAPGG HELSCDFWEL IGLAPAGGAD NLINEESDVD VQLNNRHMMI RGENMSKILK ARSMVTRCFR DHFFDRGYYE VTPPTLVQTQ VEGGATLFKL DYFGEEAFLT QSSQLYLETC LPALGDVFCI AQSYRAEQSR TRRHLAEYTH VEAECPFLTF DDLLNRLEDL VCDVVDRILK SPAGSIVHEL NPNFQPPKRP FKRMNYSDAI VWLKEHDVKK EDGTFYEFGE DIPEAPERLM TDTINEPILL CRFPVEIKSF YMQRCPEDSR LTESVDVLMP NVGEIVGGSM RIFDSEEILA GYKREGIDPT PYYWYTDQRK YGTCPHGGYG LGLERFLTWI LNRYHIRDVC LYPRFVQRCT P.

Q&A

What is NARS and how does it relate to human cognition?

NARS (Non-Axiomatic Reasoning System) is an adaptive reasoning system designed for learning under uncertainty. Unlike traditional AI systems that depend on predefined axioms or extensive data training, NARS operates on the principle of experience-grounded semantics and employs a unified framework for reasoning, learning, memory, and perception .

The methodological approach to understanding NARS involves:

  • Examining its operational logic: NARS utilizes a term-oriented language Narsese and inference rules that enable it to derive new relationships from known ones

  • Analyzing its memory structures: NARS employs a concept-centered memory organization that allows for dynamic knowledge representation

  • Studying its control mechanisms: NARS prioritizes tasks based on their urgency and importance, similar to attention allocation in human cognition

  • Evaluating its adaptability: NARS can incorporate new knowledge and revise existing beliefs based on new evidence, mirroring human cognitive flexibility

NARS models human cognition by implementing key cognitive functions within a unified system rather than as separate modules, aligning with the integrated nature of human mental processes .

What is Arbitrarily Applicable Relational Responding (AARR) in the context of NARS?

Arbitrarily Applicable Relational Responding (AARR) refers to the learned human ability to relate symbols in flexible, context-dependent ways—a cornerstone of human language and reasoning. In the context of NARS, AARR is modeled through integration with principles from Relational Frame Theory (RFT) .

The methodological approach to implementing AARR in NARS involves:

  • Establishing relational frames: Training NARS to recognize specific types of relations (e.g., equivalence, opposition) between stimuli

  • Implementing mutual entailment: Enabling bidirectional derivation of relations (e.g., if A→B, then B→A)

  • Developing combinatorial entailment: Programming NARS to infer indirect relations from explicitly trained ones (e.g., from A→B and B→C, deriving A→C)

  • Incorporating contextual control: Adding mechanisms that allow context to determine which relations apply in specific situations

  • Enabling transformation of function: Implementing function transfer across related stimuli without additional direct training

Research demonstrates that NARS can successfully model these AARR phenomena, illustrating that sophisticated relational reasoning is achievable through adaptive symbolic systems without extensive datasets .

How does NARS implement learning processes similar to human learning?

NARS implements learning processes that parallel human learning through several key mechanisms:

  • Experience-based knowledge acquisition: Rather than beginning with comprehensive knowledge, NARS builds understanding incrementally through exposure to examples and cases

  • Inductive reasoning: NARS can generalize from specific instances to broader principles, similar to how humans form conceptual categories

  • Contextual learning: The system can take context into account by treating it as information in the premise of statements or rules

  • Revision of beliefs: NARS can update its knowledge base when confronted with new evidence, adjusting confidence levels in existing beliefs

  • Transfer learning: Through mechanisms like transformation of stimulus function, NARS can apply knowledge learned in one context to novel situations

Research methodology for studying these learning processes typically involves:

  • Pretraining phases to establish foundational relational skills

  • Conditional discrimination training using protocols like Matching-to-Sample (MTS)

  • Function training to assign specific responses to stimuli

  • Testing phases to evaluate derived relations and knowledge transfer

For example, in experimental studies, NARS has demonstrated the ability to learn identity matching tasks and subsequently generalize identity relations to novel stimuli, exhibiting an emergent form of relational reasoning similar to human learning .

How can researchers design experiments to evaluate stimulus equivalence and transfer of function in NARS?

Designing experiments to evaluate stimulus equivalence and transfer of function in NARS requires a methodical approach that mirrors protocols used in human behavioral research while accounting for computational implementation. Based on the Hayes et al. (1987) methodology referenced in the research , a comprehensive experimental design would include:

  • Pretraining phase:

    • Explicitly establish foundational relational skills

    • Train symmetry relations (X1→Y1 and Y1→X1)

    • Train transitivity relations (X1→Y1, Y1→Z1, deriving X1→Z1)

    • Document training trials with precision metrics including frequency, confidence values, and derivation paths

  • Conditional discrimination training:

    • Implement Matching-to-Sample (MTS) procedure

    • Create distinct stimulus networks (e.g., A1-B1-C1 and A2-B2-C2)

    • Train direct relations within networks (A1→B1, B1→C1)

    • Establish control conditions for comparison

    • Record system responses and adaptation patterns

  • Function training:

    • Assign discriminative responses to specific stimuli (e.g., ^clap for B1, ^wave for B2)

    • Establish stable response patterns through reinforcement

    • Vary reinforcement schedules to test robustness

  • Testing derived relations and transfer:

    • Test for bidirectional relations without additional training

    • Examine combinatorial entailment within networks

    • Evaluate transfer of functions to equivalent stimuli (e.g., does C1 trigger ^clap response?)

    • Measure response latency and confidence values

Data analysis should include comparison of derived relation accuracy against chance performance, documentation of inference chains using NARS's logical notation, analysis of confidence values across derived vs. directly trained relations, and evaluation of contextual sensitivity in function application .

How do emotional mechanisms in NARS relate to human emotional processing?

The implementation of emotional mechanisms in NARS draws direct inspiration from mammalian basic emotions or "affects," establishing a biologically plausible approach to modeling affective influence on cognition . This represents an important frontier in developing AI systems that more closely approximate human-like cognitive-affective integration.

Methodological approaches to researching NARS emotional mechanisms include:

  • Biological homology mapping:

    • Identifying functional equivalents of mammalian emotional systems in NARS

    • Drawing parallels between neurobiological emotional circuits and computational control structures

    • Establishing operational definitions of basic emotions within the NARS framework

  • Implementing affective influence on cognitive processing:

    • Modeling how emotions modulate attention allocation and resource distribution

    • Programming emotional states to influence goal prioritization

    • Designing emotional valence systems that impact memory encoding and retrieval

    • Creating feedback loops between cognitive outcomes and emotional states

  • Experimental validation:

    • Designing comparative studies between human emotional responses and NARS emotional processes

    • Creating scenarios that trigger specific emotional responses

    • Measuring impact of emotional states on reasoning efficiency and decision quality

    • Testing interventions that regulate emotional processing

Research challenges in this domain include capturing the subjective qualitative aspects of emotions within a computational framework, establishing appropriate balance between emotional influence and rational processing, and determining how to implement emotional learning that adapts appropriately over time .

What methodological approaches best demonstrate opposition frames and transformation of function in NARS?

Opposition frames represent a more complex relational phenomenon than simple equivalence relations, requiring sophisticated experimental designs to properly evaluate NARS's capabilities in this domain. Based on research inspired by Roche et al. (2000) , methodological approaches for investigating opposition frames and transformation of function should include:

  • Relational frame pretraining:

    • Establish explicit "SAME" and "OPPOSITE" relations

    • Train mutual entailment patterns specific to opposition (if A is OPPOSITE to B, then B is OPPOSITE to A)

    • Develop combinatorial entailment for opposition frames (if A is SAME as B and B is OPPOSITE to C, then A is OPPOSITE to C)

    • Create protocols for mixed relation networks (combinations of SAME and OPPOSITE relations)

  • Network construction methodology:

    • Design comprehensive relational networks with multiple stimuli (e.g., A1-B1-C1, A2-B2-C2)

    • Implement Matching-to-Sample procedures to establish explicit SAME and OPPOSITE relations

    • Document training sequences and reinforcement schedules

    • Establish relationship verification protocols

  • Function assignment and assessment:

    • Train specific responses to key stimuli (e.g., ^clap for B1, ^wave for B2)

    • Design test sequences that require transformation across opposition frames

    • Create measurement protocols for response accuracy, confidence, and latency

    • Implement contextual cues that modulate relational responding

Research using these methodologies has demonstrated that NARS can successfully model contextually controlled transformations of function within opposition frames, confirming that its logical framework is sufficiently powerful to capture these complex relational phenomena .

What does research data reveal about NARS performance in stimulus equivalence tasks?

Research data from theoretical experiments on stimulus equivalence in NARS provides valuable insights into system performance and capabilities. Based on the experiments described in the literature , we can analyze key performance indicators:

Performance AspectObservationImplication
Mutual EntailmentSuccessfully derived bidirectional relations (if trained A→B, inferred B→A)Demonstrates basic symmetry capabilities fundamental to equivalence relations
Combinatorial EntailmentCorrectly inferred indirect relations from explicitly trained ones (from A→B and B→C, inferred A→C)Shows capacity for transitive inference essential for complex relational networks
Confidence ValuesHigher confidence in directly trained relations compared to derived relationsMirrors human tendency to show stronger certainty for explicitly learned information
Function TransferDiscriminative functions (e.g., ^clap, ^wave) initially trained on B-stimuli were transferred to C-stimuliDemonstrates successful transformation of stimulus function through equivalence relations
Contextual ControlResponded differentially based on relational contextShows ability to modulate responses based on contextual cues

These results illustrate that NARS logic effectively models complex relational learning phenomena essential for modeling human-like symbolic reasoning and cognition . The data analysis methodology involved examining logical derivation pathways within the NARS system, response patterns to novel stimulus arrangements, transfer of trained functions across related stimuli, and confidence values associated with different types of derivations.

How can researchers implement and evaluate opposition frames in NARS experiments?

Implementation and evaluation of opposition frames in NARS requires sophisticated experimental designs and analysis methodologies that can capture the complexities of this relational phenomenon. Based on research inspired by Roche et al. (2000) , a comprehensive approach would include:

Implementation Methodology:

  • Explicit frame training:

    • Establish "SAME" and "OPPOSITE" relations through direct training

    • Train mutual entailment for both relation types

    • Develop combinatorial entailment across mixed relation networks

    • Implement contextual cues that signal which relation applies

  • Network construction protocol:

    • Design comprehensive relational networks (e.g., A1-B1-C1, A2-B2-C2)

    • Establish explicit SAME and OPPOSITE relations between key stimuli

    • Create balanced networks to control for order effects

    • Implement methodical training sequences with verification steps

Evaluation Framework:

Evaluation DimensionMethodologySuccess Criteria
Mutual EntailmentTest derivation of bidirectional opposite relationsSystem correctly derives that if A is opposite to B, then B is opposite to A
Combinatorial EntailmentTest derivation across relation types (e.g., SAME+OPPOSITE chains)System correctly derives that SAME+SAME=SAME, SAME+OPPOSITE=OPPOSITE, OPPOSITE+OPPOSITE=SAME
Function TransformationTest transfer of functions through opposition framesFunctions transfer with appropriate transformation (e.g., if B1→^clap and A1 is OPPOSITE to B1, then A1→^wave)
Contextual ControlTest response patterns with varying contextual cuesSystem's relational responding is appropriately modulated by contextual signals

Research data demonstrates that NARS can successfully model contextually controlled transformations of function across opposition frames, confirming that its logical framework can capture these complex relational phenomena .

What are the implications of NARS for developing Artificial General Intelligence?

The theoretical demonstration of AARR within NARS has significant implications for Artificial General Intelligence (AGI) research, presenting an alternative pathway to developing systems with human-like cognitive capabilities .

Methodological considerations for exploring NARS's implications for AGI include:

  • Comparative analysis with current AI paradigms:

    • Evaluating NARS's "small data" approach against deep learning's massive data requirements

    • Comparing contextual flexibility of NARS with context handling in transformer-based models

    • Assessing logical consistency maintenance across varied domains

    • Measuring generalization capabilities from limited examples

  • Scalability research:

    • Testing NARS's reasoning capabilities across increasingly complex domains

    • Evaluating computational efficiency as knowledge base expands

    • Assessing integration potential with complementary AI approaches

    • Measuring performance degradation under resource constraints

  • Cross-domain generalization:

    • Designing experiments that require knowledge transfer between unrelated domains

    • Creating novel problem-solving scenarios that weren't explicitly trained

    • Implementing meta-learning capabilities within the NARS framework

    • Evaluating autonomous goal setting and revision

The research demonstrates that sophisticated relational reasoning is achievable through adaptive symbolic systems without relying on extensive datasets, reinforcing structured symbolic learning as a viable path toward AGI . This research direction suggests that AGI development may benefit from focusing on implementing core relational reasoning capabilities and contextual flexibility rather than primarily scaling up model size and training data.

What research challenges exist in integrating Relational Frame Theory with NARS?

Integrating Relational Frame Theory (RFT) with NARS presents several significant research challenges that require innovative methodological approaches :

Research ChallengeDescriptionMethodological Approaches
Representational AdequacyEnsuring NARS can represent the full range of relational frames described in RFTDevelop formal notations for each frame type; Create systematic implementation protocols; Design verification experiments for each frame type
Contextual ControlImplementing flexible contextual control mechanisms that determine which relations apply in specific situationsDesign contextual encoding systems; Develop context-sensitive inference rules; Create experimental protocols with varying contextual cues
Derivation ComplexityManaging computational complexity as relational networks grow in size and interconnectednessDevelop optimization strategies; Implement attention mechanisms; Create pruning algorithms for less relevant relations
Transformation GeneralityEnsuring that transformation of function works across all relation types and combinationsDesign comprehensive test batteries; Develop transformation rules for complex relations; Create cross-domain validation protocols
Developmental TrajectoryModeling the acquisition of relational abilities in a sequence similar to human developmentImplement staged learning protocols; Create curriculum-based training sequences; Design longitudinal evaluation frameworks

Addressing these challenges requires interdisciplinary collaboration between RFT researchers, AI developers, cognitive scientists, and philosophers of mind. The integration of these approaches holds promise for advancing both our understanding of human cognition and the development of more human-like artificial intelligence systems .

Product Science Overview

Structure and Function

AsnRS belongs to the class II aminoacyl-tRNA synthetases (aaRS), which are characterized by their unique structural motifs and catalytic mechanisms . The human recombinant form of AsnRS is produced in Escherichia coli and consists of a single, non-glycosylated polypeptide chain containing 571 amino acids . This recombinant protein has a molecular mass of approximately 65.3 kDa and includes a 23 amino acid His-tag at the N-terminus for purification purposes .

Genetic and Molecular Characteristics

The gene encoding human cytosolic AsnRS is known as NARS1 . The cDNA sequence of NARS1 contains an open reading frame encoding 548 amino acids . The protein sequence of human AsnRS shares significant identity with homologous enzymes from other species, such as Brugia malayi and Saccharomyces cerevisiae .

Expression and Purification

Human recombinant AsnRS is expressed in E. coli as a fusion protein with an N-terminal calmodulin-binding peptide . The recombinant protein is purified using affinity chromatography techniques, ensuring high purity and functionality . The purified AsnRS efficiently catalyzes the aminoacylation of tRNA, confirming its biological activity .

Clinical and Research Applications

AsnRS has been identified as a human autoantigen, meaning it can trigger an immune response in certain autoimmune diseases . This property makes it a valuable target for research into autoimmune disorders and potential therapeutic interventions. Additionally, the recombinant form of AsnRS is used in various biochemical and structural studies to understand its role in protein synthesis and its interactions with other cellular components .

Storage and Stability

The human recombinant AsnRS is typically stored at -20°C to maintain its stability and activity over extended periods . For short-term use, it can be stored at 4°C. To prevent degradation, it is recommended to avoid multiple freeze-thaw cycles and to add a carrier protein, such as human serum albumin (HSA) or bovine serum albumin (BSA), for long-term storage .

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