The TANK gene (Chromosome 2, locus 2q24.2) encodes a cytoplasmic scaffold protein composed of 425 amino acids in its longest isoform. Structural studies reveal that TANK lacks enzymatic activity but contains multiple interaction domains, including:
TANK forms homodimers and heterodimers with adaptor proteins, enabling its role as a signaling node .
TANK modulates NF-κB and interferon regulatory factor (IRF) pathways by interacting with key signaling molecules:
TANK deficiency in mice (Tank −/−) leads to:
Hyperactive TLR/BCR signaling: Elevated IL-6, TNF-α, and IgG/IgM autoantibodies .
Lupus-like autoimmunity: Spontaneous nephritis, splenomegaly, and CD138+ plasma cell expansion .
Enhanced TRAF6 ubiquitination: Uncontrolled NF-κB and AP-1 activation .
Key phenotypes observed in Tank −/− mice:
Parameter | Wild-Type | TANK-Deficient |
---|---|---|
Serum IL-6 (post-R848) | 1.2 ng/mL | 4.8 ng/mL |
Splenic B cells | 40% CD19+ | 62% CD19+ |
Autoantibody levels | Baseline | 6.2-fold increase |
Nephritis incidence | 0% | 85% by 6 months |
These findings underscore TANK’s non-redundant role in restraining excessive immune activation .
Dysregulated TANK expression or function is linked to:
Autoimmune diseases: Lupus-like pathologies due to unchecked TLR/BCR signaling .
Viral infections: Epstein-Barr virus exploits TANK-TRAF interactions to evade immune detection .
Cancer: Overactive TBK1/IKKε in TANK-deficient microenvironments may promote tumor survival .
Pharmacological targeting of TANK-TBK1 interactions (e.g., inhibitors blocking TBK1 activation) is under investigation for autoimmune and inflammatory disorders .
How post-translational modifications (e.g., phosphorylation) regulate TANK’s scaffold activity.
Tissue-specific roles of TANK in stromal versus immune cells.
Potential compensatory mechanisms involving homologous adaptors (e.g., NAP1, SINTBAD).
Demographic categorization in human studies should follow established scientific frameworks while remaining appropriate to your specific research objectives. Standard practice often defines "young" subjects as ages 19-40 years and "older" subjects as 41-79 years, though these boundaries should be justified based on your research questions .
When establishing demographic categories, researchers should:
Clearly document and justify age boundaries in methodology sections
Consider biological or physiological mechanisms related to demographic factors
Ensure sufficient sample sizes within each category for statistical power
Account for potential covariates that correlate with demographic variables
For comprehensive demographic documentation, use structured tables:
Demographic Category | Subcategory | Participants | Percentage |
---|---|---|---|
Gender | Male | 13 | 52% |
Female | 12 | 48% | |
Age | Young (19-40) | 14 | 56% |
Older (41-79) | 11 | 44% | |
Ethnicity | Caucasian | 7 | 28% |
African American | 6 | 24% | |
Asian | 6 | 24% | |
Hispanic | 6 | 24% |
This demographic structure enables meaningful comparisons while maintaining statistical validity and relevance to existing literature .
When collecting human biological samples for TANK Human research, standardized protocols are essential for ensuring data quality and reproducibility:
Obtain IRB approval for all protocols involving human subjects
Secure signed consent forms prior to any sample collection
Sample from standardized anatomical locations (e.g., upper back and forearm)
Use appropriate collection techniques for your target compounds
Process samples consistently following validated methodologies
For example, when analyzing volatile organic compounds (VOCs), samples might be concentrated to approximately 50 μL on a rotary evaporator, with 5 μL of each sample then injected into analytical systems such as GC/MS and GC/FPD .
Researchers should document all deviations from standard protocols and maintain consistent processing conditions across all samples to ensure valid comparisons between experimental groups.
Ethical considerations in TANK Human research must be comprehensively addressed throughout the research process:
Obtain Institutional Review Board (IRB) approval for all protocols
Develop clear informed consent documents explaining study purpose, procedures, risks, and benefits
Implement robust privacy protection and confidentiality measures
Provide appropriate subject compensation that is non-coercive
Establish special protections for vulnerable populations
Design secure data management systems for storing and sharing information
Develop protocols for reporting and addressing adverse events
Allow participants to withdraw without penalty
As noted in published research, all protocols should be "approved by the University Institutional Review Board (IRB) for Research Involving Human Subjects" with subjects "asked to read and sign IRB-approved consent forms before starting the study protocol" . Documentation of ethical procedures should be maintained throughout the research process and reported in publications.
Sample pooling in TANK Human studies requires careful methodological consideration:
Determine pooling rationale based on research questions and sample volume constraints
Define clear demographic or condition-based categories for pooling
Use standardized volumes from each individual sample (e.g., 100 μL from each subject)
Ensure thorough mixing of pooled samples (e.g., vortexing) for homogeneity
For example, in studies of volatile organic compounds from human skin, researchers have divided samples into categories like "young male (≤ 40 years), older male (> 40 years), young female (≤ 40 years) and older female (> 40 years)" with equal volumes from each subject placed into the appropriate pool .
While pooling offers advantages for examining group-level differences and compensating for limited sample volumes, researchers should recognize limitations:
Loss of individual variation information
Potential masking of outliers
Reduced ability to detect individual-level correlations
When reporting pooled analyses, clearly document pooling methodology and rationale in research publications.
Comprehensive documentation of subject characteristics is essential for TANK Human research integrity:
Collect demographic data through standardized questionnaires
Document inclusion/exclusion criteria with clear justification
Record relevant physiological parameters using calibrated instruments
Maintain detailed records of sampling conditions and methodologies
Create a master database linking subject characteristics to sample identifiers
When presenting subject characteristics in publications, use structured tables that include:
Sample size calculations and recruitment targets
Demographic composition across all relevant variables
Physiological parameters relevant to the research question
Inclusion/exclusion criteria with numbers of subjects excluded per criterion
Statistical comparison of subject groups to verify appropriate matching
This level of documentation enhances reproducibility and enables meaningful interpretation of research findings across different studies .
For TANK Human studies with multiple variables, structured experimental design approaches enhance both validity and efficiency:
Implement a wizard-like tool (such as SMAC system) to systematically guide the experimental process
Define up to three critical design factors representing experimental dimensions
Structure each factor with characteristics that allow appropriate design generation
Incorporate within-cell observations that can be collapsed across sets of observations
The experimental design structure should directly inform:
Data collection protocols and variable measurements
Statistical analysis approaches appropriate to the design
Participant allocation to experimental conditions
Sequencing of experimental manipulations
As noted in research on human-in-the-loop simulation studies, the "experimental design wizard" approach allows researchers to "define the various dimensions of the study" in a way that provides "the necessary inputs to create a data collection and analysis structure" .
This systematic approach to experimental design helps researchers avoid common pitfalls and ensures that the resulting data structure is appropriate for statistical analysis.
Outlier management in TANK Human biological samples requires a systematic approach:
Detection Methods:
Visual inspection of data distributions (boxplots, histograms)
Statistical identification using standardized measures
Subject-matter expertise to identify biologically implausible values
Investigation Process:
Examine potential measurement or recording errors
Verify sample handling procedures for each outlier case
Consider biological explanations for extreme values
Management Strategies:
Implement methods that eliminate "obvious exogenous materials from unwanted sources"
Recognize that while tedious, methods that carefully screen for contamination are "far less prone to the influence of outlier values from large exogenous components"
Document all outlier investigations and decisions
When analyzing volatile organic compounds, for example, researchers calculate "the relative percentages of selected compounds" after carefully eliminating exogenous materials that could represent outliers .
This balanced approach maintains data integrity while preventing distortion of results from non-representative extreme values.
Validating experimental design effectiveness in TANK Human studies requires a comprehensive approach:
Design Validation:
Use structured experimental design tools to generate appropriate designs
Limit experimental dimensions to a manageable number (typically three or fewer)
Define clear factor characteristics for design generation
Implementation Validation:
Facilitate "coordination and communication between the experimental design and simulator operator"
Verify that all necessary components are available before study initiation
Track which subjects have completed which conditions
Analysis Validation:
Conduct both automated and manual data analysis
Verify statistical assumptions appropriate to the chosen analyses
Ensure analyses match the experimental design structure
Reporting Validation:
Generate structured reports following standardized templates
Include comprehensive documentation of methods and results
Supplement with additional analyses as warranted by findings
This validation approach helps "avoid some design pitfalls" while ensuring rapid and accurate execution of the experimental protocol .
Investigating potential contaminants in TANK Human biological samples requires systematic detection and elimination approaches:
Prevention Strategies:
Implement standardized collection protocols with appropriate controls
Use reference samples to establish baseline measurements
Document potential environmental contaminant sources
Detection Methods:
Apply specialized analytical techniques like gas chromatography with flame photometric detection (GC/FPD) for sulphur compounds
Monitor known contaminant markers in samples
Compare test samples against blank controls
Elimination Approaches:
Develop methods that are "far less prone to the influence of outlier values from large exogenous components"
Ensure "all obvious exogenous materials from unwanted sources are eliminated"
Apply compound-specific analytical techniques for suspected contaminants
Analysis Considerations:
Calculate relative percentages of compounds after contaminant elimination
Examine differences in compound profiles between demographic groups
Document all contaminant identification and elimination procedures
For example, when analyzing volatile organic compounds from human skin, researchers might focus on specific compounds like "dimethylsulphone, benzothiazole, C8-C10 aldehydes" and others, while carefully eliminating exogenous contaminants .
This systematic approach enhances the validity of biological sample analysis by distinguishing endogenous compounds from contaminants.
Structuring the experimental process in TANK Human studies requires a comprehensive framework:
Experimental Design Phase:
Implement "an experimental process wizard that guides the user through the process of designing, configuring, running, analyzing, and reporting"
Define experimental dimensions and factor characteristics
Determine appropriate statistical analyses that match the design
Experiment Configuration:
Configure experimental conditions based on the design
Establish data collection protocols and measurement techniques
Create standardized scripts for participant instructions
Experiment Execution:
Determine "in what order to run subjects and which experimental conditions should be used for each run"
Track participant progress through the experimental protocol
Verify data quality throughout the collection process
Data Analysis:
Initiate "statistical data analysis and review the results"
Perform both automated analyses matching the experimental design
Conduct "ad hoc analyses as desired" to explore unexpected findings
Reporting:
Create structured reports using standardized templates
Include comprehensive documentation of methods and results
Export results "to a document along with other template report sections"
Ensure complete documentation of all methodological decisions
This structured approach provides "a common point of reference and indicates the status of the experiment," enhancing both validity and reproducibility .
Analyzing variations in TANK Human biological compounds across demographic groups requires systematic analytical approaches:
Sample Preparation:
Pool samples strategically by demographic characteristics (age, gender, ethnicity)
Use standardized volumes from each subject (e.g., 100 μL per subject)
Process samples consistently to minimize methodology-based variations
Compound Selection:
Identify target compounds through initial screening of chromatograms
Select compounds that "appeared to vary in many chromatograms"
Include compounds with known biological significance (e.g., dimethylsulphone as "a well-known metabolite in human body fluids")
Analysis Methods:
Calculate relative percentages of selected compounds for each demographic group
Examine differences related to age, gender, and anatomical location
Apply statistical tests appropriate to the data distribution and study design
Visualize variations through comparative chromatograms or concentration tables
Interpretation Framework:
Consider biological significance of observed variations
Relate findings to existing literature on metabolite differences
Acknowledge limitations in sample pooling and compound selection
Propose mechanisms for observed demographic differences
For example, researchers analyzing volatile organic compounds from human skin found that compounds like "benzothiazole, methoxy acetic acid dodecyl ester and isopropyl palmitate" showed differences "attributed to age or emanation site" .
This systematic approach allows researchers to identify meaningful biological variations across demographic groups while maintaining methodological rigor.
TANK is classified as a protein-coding gene and is associated with several biological pathways, including the Toll-Like Receptor 3 (TLR3) Cascade and the TNFR1 Pathway . It is involved in the activation of the NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) signaling pathway, which is essential for immune response regulation .
The activity of TANK is regulated through its interactions with TRAF proteins and other components of the NF-κB signaling pathway. These interactions ensure the proper regulation of immune responses and the prevention of excessive inflammation .
In summary, TRAF Family Member-Associated NFKB Activator (Human Recombinant), or TANK, is a critical protein involved in the regulation of immune responses and inflammation. Its role in the NF-κB signaling pathway highlights its importance in maintaining immune system balance and preventing inflammatory diseases.