Search Results (152)

Supraventricular tachycardias (SVTs), including atrial fibrillation (AF), atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entrant tachycardia (AVRT), and focal atrial tachycardias, can possibly arise from the interaction of genetic predisposition and environmental exposures. While genome-wide association studies (GWASs) have identified 525 loci for atrial fibrillation and a small number of loci for AVNRT and accessory pathway-mediated tachycardia, the contribution of air pollution, lifestyle factors and psychosocial stress to epigenetic remodeling of atrial tissue remains insufficiently integrated into current mechanistic models of arrhythmogenesis. This review aims to synthesize evidence on how environmental exposures, including PM_2.5, NO₂, ozone, tobacco smoke, obesity, alcohol use, and physical inactivity, modulate epigenetic pathways relevant to SVT susceptibility, and to evaluate whether AF-derived epigenetic insights can be extrapolated to other SVTs. Thus, a narrative synthesis was conducted across studies examining environmental determinants, epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs), and genetic susceptibility in SVTs. Literature from cardiac tissue studies, circulating epigenetic biomarker analyses, and mechanistic AF models was integrated to construct a unified gene–environment–epigenome framework. In atrial fibrillation, environmental exposures are consistently associated with epigenetic alterations affecting atrial electrophysiology, inflammation, oxidative stress and structural remodeling, and air pollutants and lifestyle factors modulate methylation signatures, histone-modifying enzymes and microRNA networks implicated in atrial conduction and re-entry. For AVNRT, AVRT and focal atrial tachycardia the evidential position is different. Large prospective cohort and case-crossover analyses now link air pollution to incident and acute supraventricular tachycardia, and genome-wide association studies have identified susceptibility loci for AVNRT and for accessory-pathway-mediated tachycardia, including one gene encoding a cardiac chromatin-remodeling protein; but no epigenomic profiling of nodal or accessory-pathway tissue has been reported, and no study has measured an environmental exposure, an atrial epigenetic mark and a non-AF SVT endpoint in the same participants. Twin data indicate that approximately 35% of SVT risk is attributable to genetic and 65% to unique environmental factors, which motivates a gene–environment–epigenome framework without validating its mechanistic detail outside AF. Mapping GWAS-identified loci onto environmentally responsive regulatory pathways identifies candidate convergence points between inherited risk and exposure-driven remodeling; for non-AF SVT, these are designated working hypotheses rather than established mechanisms. Air pollution and lifestyle factors are associated with supraventricular arrhythmia across the spectrum, and in atrial fibrillation there is direct evidence that they act, in part, through epigenetic reprogramming of atrial tissue. No epigenetic panel has been prospectively validated for the prediction of any supraventricular arrhythmia, and precision risk stratification therefore remains a research objective rather than a near-term clinical horizon. Integrating environmental exposure data with genetic and epigenomic profiling is nonetheless the most plausible route toward it. Future priorities include exposure-stratified, cell-resolved epigenomic profiling of atrial and nodal tissue, prospective validation of candidate circulating markers against incident arrhythmia, and replication in non-European populations and in both sexes. Full article

Rnd3 is an atypical member of the Rho GTPase family whose activity is mainly regulated by expression, localization and protein stability rather than canonical GDP/GTP cycling. In cancer, Rnd3 has been described both as a tumor suppressor and as a tumor-promoting factor, creating an apparent functional paradox. We propose that this paradox is resolved by a mechanistic invariant: Rnd3 exerts a conserved inhibition of RhoA/ROCK1-dependent actomyosin contractility, whose phenotypic output is redirected by context-specific accessory effectors rather than reversed. In this review, we revisit this paradox by integrating evidence from mechanistic studies, tumor models and patient-associated datasets. We propose that Rnd3 should not be interpreted through a binary oncogene/tumor-suppressor framework, but rather as a context-dependent regulator of tumor cell state. In many tumor settings, Rnd3 repression or loss of Rnd3 function favors proliferation, apoptosis resistance and therapy resistance through pathways involving Notch, NF-κB, EGFR/ERK, EZH2-dependent chromatin regulation, m6A-mediated RNA control, microRNAs and chaperone-mediated autophagy. However, in selected contexts, including RTK-driven glioblastoma, hepatocellular carcinoma, non-small-cell lung cancer, melanoma and gastric cancer, Rnd3 may support tumor fitness, migration or invasive plasticity. We therefore propose a functional stratification model in which Rnd3 output depends on the biological process, tumor lineage, pathway activity and mechanical state of the cell. Full article

Cucurbitacins are highly oxygenated tetracyclic triterpenoids characterized by intense bitterness, substantial structural diversity, and important consequences for plant–herbivore interactions. Although best known from Cucurbitaceae, cucurbitacins and related cucurbitane-type metabolites also occur in phylogenetically distant herbaceous and woody plants. Genetic and biochemical studies have validated several core biosynthetic steps, including cucurbitadienol formation by oxidosqualene cyclases and subsequent modification by cytochrome P450 monooxygenases, acyltransferases, and glycosyltransferases. Tissue-preferential basic helix–loop–helix transcription factors constitute the best-characterized regulatory layer, whereas the evidence supporting accessory regulators, transporters, and environmental responses varies from functional validation to transcriptomic or genomic prediction. From the plant perspective, cucurbitacins deter feeding or impair performance in many generalist and non-adapted herbivores. By contrast, their use as host-recognition cues and feeding stimulants by specialist diabroticite beetles reflects evolved herbivore adaptations involving perception, tolerance, metabolism, or sequestration rather than a second defensive function of the plant trait. Herbivore-induced cucurbitacin accumulation has been demonstrated in particular systems, although its regulatory mechanisms and ecological generality remain unresolved. Unlike previous reviews centered primarily on cucurbitacin chemistry, pharmacological activity, or individual biosynthetic pathways, this review integrates evidence-graded pathway reconstruction and molecular regulation with taxonomic distribution, insect adaptation, domestication, and agroecological consequences. Mechanistically, this review traces how scaffold formation, oxidative tailoring, conjugation, tissue-specific regulation, and transport give rise to contrasting ecological outcomes through herbivore-specific perception, tolerance, metabolism, and sequestration. We conclude that uniformly increasing or eliminating cucurbitacins is unlikely to provide broadly effective crop resistance because either direction may favor a different herbivore group. Future priorities include functional validation of candidate genes, spatially resolved metabolite analysis, comparative investigation of non-cucurbit lineages, and field evaluation involving generalist and specialist herbivores, crop quality, and non-target organisms. These advances will support context-specific fruit-quality improvement, behavioral pest control, and integrated pest management strategies rather than cucurbitacin manipulation as a stand-alone resistance approach. Full article

Both RIT1 and RIT2 are members of the RAS superfamily of small GTPases, which regulate various cellular processes. RIT1 is widely expressed, whereas RIT2 is primarily found in neuronal tissues. Dysregulation of these proteins has been associated with several human diseases, including Noonan syndrome, cancer, Parkinson’s disease, autism, and schizophrenia. Although RIT1 and RIT2 are often compared to classical RAS proteins, they exhibit distinct regulatory and biochemical properties. Here, we demonstrate that RIT1 differs from classical RAS in GTPase cycling. Unlike classical RAS proteins, RIT1 did not respond to SOS1-mediated nucleotide exchange or p120GAP-stimulated GTP hydrolysis under cell-free conditions. These results imply that RIT1 may depend on regulatory mechanisms that differ from those of classical RAS proteins. However, the relevant physiological regulators remain unknown. Disease-associated RIT1 mutations cluster around the P-loop and Switch II regions. In this transient overexpression screening system, however, these mutations had only a modest effect on the canonical MAPK, PI3K/AKT, and JNK signaling pathways in HEK293T overexpression experiments. This suggests the existence of additional context-specific effectors and regulatory factors. We demonstrate that RIT1 and RIT2 interact with membrane lipids via a basic C-terminal extension. The KRLK-containing region contributes to the binding of phosphatidylserine and phosphoinositides. Charge-reversal mutations disrupt lipid interactions and liposome binding, supporting the functional importance of this region. In a reconstituted liposome system, galectin-3 and LZTR1, but not galectin-1, reduced the interaction of GDP-loaded RIT1 and RIT2 with liposomes. These results suggest that accessory proteins may influence RIT membrane interactions. However, their cellular relevance requires further validation. Together, our findings provide biochemical insights into RIT GTPase regulation and its interactions with membrane lipids under cell-free conditions. Full article

Mycobacterium tuberculosis (M. tb) possesses a unique, lipid-rich cell envelope that is critical for virulence, drug resistance, and persistence. Here, we identify the PPE family protein PPE57 as a key regulator of mycolic acid transport and host lipid exploitation. PPE57 physically interacts with the essential lipid transporter MmpL3, promoting trehalose monomycolate (TMM) translocation, enhancing trehalose dimycolate (TDM) synthesis, and increasing cell wall lipid content. Site-directed mutagenesis identified G175 as a critical residue for PPE57-MmpL3 binding. Deletion of PPE57 reduces cell wall thickness, alters lipid composition, and impairs biofilm formation. Mechanistically, PPE57 facilitates bacterial cholesterol acquisition, and during infection, activates the host PPAR-γ pathway in macrophages, leading to enhanced cholesterol uptake, lipid droplet accumulation, and increased intracellular triglyceride and cholesteryl ester levels. These changes provide a nutrient-rich niche that promotes bacterial survival and persistence. In a mouse model of infection, PPE57 deficiency results in reduced bacterial burden, milder lung pathology, and diminished lipid droplet-positive cell accumulation in lung tissues. These findings establish PPE57 as an essential accessory component of the MmpL3 lipid transport system, bridging mycobacterial cell wall assembly with host nutrient exploitation during persistent infection. Full article

Clade A Middle East respiratory syndrome coronavirus (MERS-CoV) spilled over from camels into humans in Saudi Arabia in 2012 and caused pneumonia and severe respiratory disease, with a 37% case fatality rate. While clade A and B viruses are closely related phylogenetically, clade B MERS-CoV strains have since outcompeted clade A strains and continue to circulate in camels and humans in the Middle East and cause outbreaks in humans. Clade C strains circulate in camels across the African continent but have not been reported to cause disease in humans. We have shown that a number of East African clade C isolates are less able to utilize the TMPRSS2-mediated pathway for viral entry in both cell lines and primary nasal epithelial cultures, which may underlie the reduced replication of East African clade C strains in humans. However, the reduced replicative capacity of West African strains in human cells appears to be independent of viral entry, suggesting an alternative basis for their attenuation. Here, we report that West African clade C MERS-CoV isolates with deletions in ORF4b encoding a key accessory protein, NS4b, induced significantly more robust interferon and inflammatory responses than clade A MERS in human respiratory cell lines and primary bronchial air–liquid interface cultures. The replication deficit for the West African strain BF785, which has a complete deletion of ORF4b, was partially rescued when RNASEL was knocked out in A549 cells. These findings demonstrate that complete loss of NS4b results in stronger innate immune activation than partial truncation and suggests that differential selection on NS4b may contribute to the varying phenotypes of clade C MERS-CoV strains circulating in African camels. Full article

Microbial remediation serves as a cost-effective and eco-friendly tactic for petroleum-contaminated sites. In real-world practices, petroleum-degrading microbial consortia display prominent superiority over single strains. To tap into their intrinsic synergistic degradation capacity, it is essential to dissect microbial commonalities, individual traits and functional complementarity for complicated bioremediation scenarios. This study applied bibliometric approaches to collect 15 well-documented representative petroleum-hydrocarbon-degrading strains, and summarized research progress via comparative genomic analysis. Pseudomonas aeruginosa, Bacillus subtilis and Rhodococcus erythropolis are the most frequently reported degraders with remarkable petroleum removal performance. Moreover, co-occurrence network analysis identifies Pseudomonas, Bacillus, Acinetobacter and Rhodococcus as core co-existing genera sustaining natural pollutant-degrading communities. Genomic evidence indicates these strains harbour abundant functional elements encoding diverse oxygenases, alcohol dehydrogenases, cytochrome P450 monooxygenases and key LuxR-, AraC- and GntR-family regulatory factors. P. aeruginosa has the highest copy numbers of catabolic enzyme genes, consistent with its outstanding degradation phenotype. Degraders from different genera exhibit high genetic heterogeneity, with accessory gene clusters significantly enriched in hydrocarbon degradation pathways. Six strains including P. aeruginosa and R. erythropolis assemble a complete gene cascade targeting recalcitrant polycyclic aromatic hydrocarbons. This work provides reliable genomic support for rational strain screening and synthetic-consortium optimization, facilitating knowledge-driven strategies for efficient petroleum bioremediation. Full article

The renin–angiotensin–aldosterone system (RAAS) is a fundamental regulator of blood pressure, electrolyte balance, fluid homeostasis, and tissue remodeling. The discovery of the prorenin receptor (PRR), the protein encoded by the ATP6AP2 gene, has substantially expanded the classical RAAS paradigm by demonstrating that prorenin possesses biological activity beyond its proteolytic conversion to renin. Binding of renin or prorenin to PRR enhances local angiotensin II (Ang II) generation while simultaneously initiating Ang II-independent intracellular signaling pathways, including ERK1/2, mitogen-activated protein kinases, PI3K/Akt, transforming growth factor-β, and nuclear factor-κB, thereby promoting inflammation, oxidative stress, fibrosis, cellular proliferation, and extracellular matrix accumulation. Beyond its receptor function, PRR serves as an essential accessory component of the vacuolar H+-ATPase (V-ATPase) complex, regulating vesicular acidification, lysosomal function, autophagy, protein trafficking, cellular metabolism, and Wnt/β-catenin signaling. These diverse functions explain its indispensable role in embryonic development, cell differentiation, and tissue homeostasis, as evidenced by the embryonic lethality associated with ATP6AP2 gene deficiency. PRR is predominantly localized to intracellular organelles, including the endoplasmic reticulum, Golgi apparatus, endosomes, lysosomes, and autophagic vesicles, although membrane-bound and soluble forms also contribute to physiological and pathological processes. Increasing evidence implies dysregulated PRR signaling in the development and progression of hypertension, cardiovascular disease, chronic kidney disease, diabetes, obesity, and other metabolic disorders. This review summarizes current advances in PRR and soluble PRR biology, discusses unresolved mechanistic and translational questions, and evaluates the potential of PRR as a biomarker and therapeutic target for cardiovascular, renal, and metabolic diseases. Full article

Flacherie is a major bacterial disease compromising silkworm health and cocoon productivity; however, the diversity and genomic features of larva-associated pathogens remain poorly characterized. In the present study, we isolated and characterized a Gram-negative bacterium, designated as Pseudomonas boreofloridensis strain RAC1, from the hemolymph of silkworm larvae with flacherie symptoms. The isolate exhibited clear swimming motility, indicating an active flagellar system. Biochemical profiling using the VITEK-2 platform revealed broad metabolic capabilities, including utilization of multiple organic acids and amino-acids, related enzymatic activities, highlighting its adaptability under nutrient-variable host conditions. Chemotaxonomic analysis using fatty acid methyl ester (FAME) profiling further supported its identity within the genus Pseudomonas. Whole-genome sequencing showed a 4.49 Mb GC-rich genome encoding diverse functional pathways related to central metabolism, aromatic compound degradation, and carbohydrate-active enzymes, suggesting strong ecological flexibility. Importantly, genomic screening identified virulence-associated gene and multiple antimicrobial resistance determinants, dominated by efflux pumps and outer membrane permeability factors. In addition, strain RAC1 contained several mobile genetic elements and three prophage regions, reflecting a highly plastic genome. Pangenome analysis across related Pseudomonas strains indicated an open pangenome, driven largely by accessory and cloud genes. Overall, P. boreofloridensis RAC1 represents a multidrug-resistant and genomically dynamic strain encoding virulence-associated genes and resistance genes. These genomic features suggest adaptive potential in host-associated environments and require further experimental investigation to evaluate its role in silkworm larval disease. Full article

Background: The urgent need for sustainable agricultural drives the search for effective microbial biostimulants. Cyanobacteria of the order Nostocales are promising candidates due to their nitrogen-fixing capabilities and bioactive secondary metabolites. However, the genomic potential of many soil strains from microorganism collection remains largely unexplored. Methods: We performed a targeted genomic screening of five cyanobacterial strains from the All-Russian Collection of Microorganisms (VKM): Nostoc commune VKM Al-35, Nostoc punctiforme VKM Al-37, Nostoc minutum VKM Al-168, Anabaena pirinica VKM Al-153, and Hassallia pseudoramosissima VKM Al-158. The workflow involved WGS, de novo assembly, and comparative metabolic profiling using KEGG, SEED, PLaBAse, antiSMASH, and RhizoSMASH to identify predicted plant growth-promoting (PGP) traits, biosynthetic gene clusters (BGCs), and rhizosphere competence mechanisms. Biosafety was evaluated via Comprehensive Antibiotic Resistance Database (CARD) and in silico toxomics screening. Results: High-quality genome assemblies were obtained for all strains (completeness > 99%). Functional annotation uncovered complete genetic machinery for nitrogen fixation, predicted phosphate mobilization, and phytohormone biosynthesis pathways. Comparative analysis revealed two distinct genomic strategies: a versatile support profile in Nostoc strains (expanded genomes and diverse accessory pathways) and a specialized stimulation profile in Anabaena and Hassallia strains (focused phytohormone pathways). Comprehensive CARD and antiSMASH screenings demonstrated an excellent biosafety profile, confirming the complete absence of regulated cyanotoxin clusters or acquired antibiotic resistance genes of clinical concern. Conclusions: This genome-based bioprospecting serves as a cost-effective pre-selection filter, providing a strong scientific rationale for downstream experimental validation of these strains. The presence of predicted gibberellin biosynthesis pathways and T6SS/T4SS secretion systems in H. pseudoramosissima VKM Al-158 represents a notable genomic feature among soil cyanobacteria. The identified genomic prerequisites suggest that these strains possess strong predictive potential for future development as safe biological resources for sustainable agriculture. Full article

Granite is a major lithology of stone-built cultural heritage across East Asia, the Iberian Peninsula, the Indian subcontinent, Egypt and Italy. Long regarded as durable, it nonetheless undergoes mineralogical, microstructural and macroscopic alteration through pathways that are mechanistically universal yet regionally distinctive in expression. This review synthesizes granite weathering within a multianalytical framework spanning mineralogy, microstructure, geochemistry, environmental drivers and conservation science. Mineral-specific reactions—feldspar hydrolysis, biotite oxidation coupled to clay-mineral genesis, iron-bearing transformations driving surface coloration, quartz-mediated thermal microcracking and accessory-mineral pathologies—are examined as coupled processes governing macroscopic decay. A suite of complementary analytical methods, including non-destructive, minimally invasive and laboratory-based techniques, delivers mechanistic and prognostic resolution unattainable by any single method. Two case settings—the tenth-century rock-carved Buddhas of Gyeongju Namsan and the urban granite of Jongmyo Shrine, Seoul—illustrate how integrated diagnostics resolve coupled decay on natural outcrops and how cumulative atmospheric exposure is recorded in monument-scale fabrics. Chemical weathering indices, environmental controls and conservation implications are unified into a single framework, and key gaps—standardization, time-resolved diagnostics, climate projection, multi-omics coupling, consolidant durability and machine learning—are articulated as a research agenda for granite heritage science. Full article

Common bean (Phaseolus vulgaris L.) is a strategic crop whose sustainable production depends on symbiosis with nitrogen-fixing bacteria. However, the composition and functional potential of the nodule microbiome in varieties adapted to semi-arid regions, such as northern Mexico, remain poorly documented. Therefore, this study evaluated the influence of host genotype on nodule-associated bacterial communities in three improved varieties (Pinto Bravo, NOD1, and Jamapa) under conventional management, using high-throughput sequencing of the V3–V4 regions of the 16S rRNA gene. Alpha and beta diversity analyses showed no significant differences among varieties, indicating a similar nodular microbiome regardless of genotype. At the phylum level, Proteobacteria and Bacteroidota predominated, suggesting a conserved microbial core. At the genus level, Rhizobium was the most abundant taxon, while non-rhizobial genera such as Acinetobacter and the JC017 lineage were also detected. Functional prediction using PICRUSt2 revealed conserved metabolic profiles, with dominant pathways associated with amino acid biosynthesis, carbon metabolism, aerobic respiration, and fatty acid biosynthesis, indicating metabolic redundancy linked to tolerance to osmotic, thermal, and oxidative stress. The results suggest that under semi-arid conditions, the symbiotic interaction is governed by mechanisms at the host species level (P. vulgaris), which ensure the recruitment of a functional core microbiome, whereas intraspecific variation among improved varieties may influence the recruitment of specific accessory taxa. Full article

Background/Objectives: Accurate localisation of manifest accessory pathways from the 12-lead electrocardiogram remains clinically relevant in Wolff–Parkinson–White syndrome, particularly for pre-procedural planning. Although purpose-built artificial intelligence models have shown promise in ECG interpretation, the reliability of general-purpose multimodal large language models for accessory pathway localisation is unknown. We evaluated two contemporary general-purpose AI systems against an electrophysiology-confirmed reference standard and assessed reproducibility across repeated analyses. Methods: In this retrospective, single-centre proof-of-concept diagnostic accuracy study, 49 consecutive patients with manifest accessory pathways confirmed during electrophysiology study/ablation were included. Anonymised pre-procedural 12-lead ECGs were compiled into a single PDF and analysed by ChatGPT 5 Thinking and Gemini 2.5 Pro using predefined EASY-WPW anatomical categories. Each model was tested in three independent context-reset runs. The primary outcome was repeated-run diagnostic accuracy against the electrophysiology-confirmed pathway location, with confidence intervals calculated using an ECG-clustered approach. Secondary outcomes included majority-vote accuracy, pathway-specific descriptive accuracy, exact output consistency, no-consensus outputs, and “unable to identify” responses. Results: Each model generated 147 repeated outputs from the same 49 ECGs. ChatGPT 5 Thinking correctly localised 28/147 outputs, corresponding to a repeated-run accuracy of 19.0% (ECG-clustered 95% CI 11.5–26.6), while Gemini 2.5 Pro correctly localised 18/147 outputs, corresponding to 12.2% accuracy (95% CI 6.8–17.7). Both models performed below the no-information majority-class baseline of 36.7%. Majority-vote accuracy was 7/49 for ChatGPT 5 Thinking and 2/49 for Gemini 2.5 Pro. Exact output consistency across all three runs was observed in 2/49 ECGs for ChatGPT 5 Thinking and 0/49 ECGs for Gemini 2.5 Pro. Complete no-consensus outputs occurred in 30/49 and 26/49 ECGs, respectively. “Unable to identify” responses were infrequent: 8/147 outputs for ChatGPT 5 Thinking and 2/147 outputs for Gemini 2.5 Pro. Pathway-specific estimates were descriptive only because of class imbalance and small subgroup denominators. Conclusions: General-purpose multimodal large language models demonstrated poor repeated-run accuracy, very low reproducibility, frequent no-consensus outputs, and limited abstention when localising manifest accessory pathways from 12-lead ECGs. These findings do not support their current clinical use for accessory pathway localisation. Future progress is more likely to come from purpose-built, signal-native, or rigorously validated multimodal cardiac AI systems. Full article

Bacteria associated with unhatched sea turtle eggs remain poorly characterized at the genomic level. This study provides genome-scale characterization of bacterial isolates recovered from unhatched green sea turtle (Chelonia mydas) eggs at Akyatan Beach—a critical nesting site in the Eastern Mediterranean. Sampling 30 nests during the nesting season, we isolated bacteria from infected eggshells and dead embryos. Following Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry(MALDI-TOF MS) identification and 16S rRNA validation, we performed whole-genome sequencing (WGS) on Citrobacter farmeri and Enterobacter cloacae, two opportunistic pathogens of significant clinical and ecological concern. High-quality draft genomes revealed remarkable metabolic versatility, particularly within carbon and nitrogen pathways. Most notably, we identified extensive resistomes including resistance to $\beta$-lactams, fluoroquinolones, and aminoglycosides, alongside virulence factors for adhesion and iron acquisition. ANI analysis confirmed high genomic similarity to clinical reference strains, comparative genomic analysis revealed a substantial accessory gene pool, suggesting potential genomic flexibility between the two isolates. These findings provide the first genome-scale insight into these pathogens in C. mydas nests, and highlighting their genomic potential for opportunistic pathogenicity. Our results advocate for integrating genomic microbial surveillance into nesting beach management through a ‘One Health’ lens. Full article

Background/Objectives: The seventh cervical vertebra (C7), the terminal segment of the cervical spine, demonstrates transitional characteristics between the cervical and thoracic regions. The transverse foramen (TF), a defining feature of all cervical vertebrae, is consistently present in C1 to C6 but shows marked variability at C7, appearing rudimentary or atypical. This study aimed to analyze the prevalence and morphology of TF of the C7 vertebra in the South African skeletal collection. The objectives of the study were to document the absence of the C7 TF, describe its morphological characteristics, and investigate associations between the C7 TF morphology and demographic factors. Methods: An exploratory osteological anatomical study appraised dry macerated C7 vertebrae. A total of six hundred and eighty-nine (n = 689) C7 vertebrae were analyzed. Frequency and descriptive statistics were used, as well as cross tabulations, to determine relationships between demographic factors and the presence or absence of a TF at C7. Results: Bilateral TF were present in 98.5% (n = 679) of vertebrae; 1.5% (n = 10) exhibited unilateral absence (4 left, 6 right). No bilateral absence was observed. The oval-oblique (toward midline) configuration was the most frequent shape bilaterally (left: 36.3%; right: 43.4%). Accessory double foramina occurred in 5.6% (left) and 8.3% (right); triple accessory foramina were rare (0.3%, right side only). Significant associations were found between TF shape and population affinity (p = 0.000, both sides) and age (p = 0.025 left, p = 0.037 right). A weak association was found between sex and right TF shape (p = 0.025). Conclusions: The findings support clinical and surgical implications for anatomical understanding of the vertebral artery, vein, and sympathetic nerve fibre pathways. The enclosed TF variation predominated, and triple accessory foramina were rare but notable. Full article