Search Results (72)

Background: Triple-negative breast cancer (TNBC) remains a major cause of cancer mortality due to its aggressive behavior, metabolic adaptability, and high therapeutic resistance. Extracellular vesicles (EVs) within the tumor microenvironment contribute to tumor progression and metastasis by transferring pro-tumorigenic cargo. While conventional Tumor Treating Fields use high-frequency alternating fields to disrupt mitosis, low-energy triple-frequency bioelectromagnetic approaches remain poorly characterized. Methods: We evaluated a device–drug strategy combining triple-frequency low-intensity electromagnetic stimulation (EMS2: 396 Hz, 285 Hz, 528 Hz) with the pleiotropic drug Fingolimod (FTY720). Treatments were tested in MDA-MB-231 and ARM-G breast cancer cells, with Paclitaxel as a positive control. Cell proliferation was assessed by MTS assay, and extracellular vesicles were isolated following individual and combination treatments. Quantitative LC-MS/MS proteomics was used to characterize treatment-induced changes in EVs cargo. Results: EMS2 reduced proliferation in both cell lines and produced morphological changes consistent with altered cell-cycle progression. EMS2 alone triggered adaptive metabolic responses, whereas combination with Fingolimod suppressed these compensatory signatures. EVs proteomics revealed combination-specific alterations associated with mitochondrial stress, ER stress, NF-κB suppression, and autophagy-associated pathways. The combination also reduced levels of metastasis- and stroma-associated proteins, including Mitogen-Activated Protein Kinase 12 (MAPK12) and collagen-associated ECM components (Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type VI Alpha 1 Chain (COL6A1), Collagen Type VI Alpha 3 Chain (COL6A3), and Matrilin 3 (MATN3)) in EVs. Bliss independence analysis identified a subset of metastasis-associated proteins suppressed in EVs beyond the level predicted by an additive model, an exploratory finding that will require further validation with dose–response and functional assays. Conclusions: Combined triple-frequency EMS2 and Fingolimod treatment altered the extracellular vesicle proteome, inducing signatures consistent with mitochondrial and endoplasmic reticulum stress, metabolic disruption, and reduced levels of metastasis-associated and stromal/ECM remodeling proteins, along with reduced proliferation. These findings suggest a coordinated anti-cancer effect of this tunable device–drug strategy, warranting further functional and in vivo validation to confirm therapeutic potential. Full article

To assess the genetic diversity and matrilineal differentiation between the Betpak-Dala (BD) and Volga–Ural (VU) populations of Saiga tatarica in Kazakhstan, this study sequenced and comparatively analyzed the complete mitochondrial genomes of both populations. Phylogenetic analyses showed that Saiga tatarica clustered with the genera Gazella, Nanger, and Eudorcas, indicating a close evolutionary relationship. Genetic diversity analysis revealed that the BD population exhibited higher nucleotide diversity than the VU population. A total of 22 haplotypes were identified based on complete mitochondrial genome sequences, and no haplotypes were shared between the two populations, indicating pronounced matrilineal genetic differentiation. Synonymous mutations predominated among protein-coding genes, with the NADH dehydrogenase subunit 2 gene (nd2) and NADH dehydrogenase subunit 5 gene (nd5) genes exhibiting high levels of variation and serving as key regions for the accumulation of genetic diversity within the mitochondrial genome. These findings enhance the understanding of the genetic diversity and matrilineal genetic structure of Saiga tatarica populations in Kazakhstan and provide valuable information for their conservation and management. Full article

Introduction: Brown trout (Salmo trutta L.) is a salmonid fish considered a genetically and geographically highly structured species. The species is catalogued as vulnerable in the Spanish Red List since 1992. Based on morphological differentiation, some authors have proposed splitting Salmo trutta into many taxa and in recent years, several binomials involving morphologically differentiated Western Mediterranean brown trout morphs have regained relevance as distinct species and are now assessed in the IUCN Red List. However, Spanish legislation still considers a single species, S. trutta, inhabiting Atlantic and Mediterranean rivers. Analyses of mitochondrial DNA variation across the species’ native range have revealed numerous matrilineal lineages and helped disentangle the phylogenetic relationships and biogeographic history of brown trout. Four largely distant evolutionary lineages defined by sequencing the mitochondrial control region (Adriatic, AD, Mediterranean, ME, Atlantic, AT and Duero, DU) are native among the Iberian brown trout populations. Stocking activities have resulted in introgressive hybridization of these native populations with non-native northern Atlantic stocks throughout the Iberian rivers and compromise the evolutionary singularities of brown trout in the Iberian Peninsula. Methodology: In this study, we compare complete mitogenomes from Iberian brown trout specimens with those from other regions, using both newly sequenced samples and whole mitogenomes from the GenBank database and estimate their divergence times relative to those observed among species of other Salmoninae genera, such as Oncorhynchus and Salvelinus, to assess patterns of species-specific divergence among Iberian brown trout populations. Results: The evolutionary relationships of the specimens using their mitogenomes fitted with previous analyses using partial mitochondrial sequences and confirmed the strong differentiation among the Iberian lineages. All the branches involving distant Iberian mitogenomes are sister branches with taxa historically described under different binomials (such as Salmo macrostigma, S. multipunctatus, S. pallaryi). Conclusions: The results provide evidence supporting the existence of potentially distinct and undescribed native Salmo species in the Iberian rivers. Full article

Prior to this study, knowledge on the evolutionary lineage of Garra remained inadequate, as previous phylogenetic investigations were primarily based on partial gene sequences. Although several mitogenomes of Garra species have been reported, their structural organization and comprehensive genomic characteristics have not been thoroughly evaluated. In this study, Garra manipurensis, endemic to the Indo-Burma biodiversity hotspot, was identified based on its detailed morphology and meristic counts. The circular mitogenome of G. manipurensis is 16,776 bp in length and contains the canonical set of 37 genes, along with duplicated control regions separated by tRNA-Proline. The comparative assessments across Garra species indicate predominantly conserved GTG start codons, occasional alternative ATA initiation codons, and incomplete stop codons. The selection pressure examinations within Garrini taxa reveal a purifying selection across all protein-coding genes. The control region comprises four conserved sequence blocks and species-specific tandem repeats, reflecting a balance between functional constraint and lineage-dependent evolutionary dynamics. The phylogenetic inference supports the monophyly of Garra and places G. manipurensis in close affinity with Garra flavatra, which is native to the western slope of Rakhine Yoma in Myanmar and Mizoram State in northeastern India. The genetic diversity analyses revealed haplotype differentiation, with shallow intraspecific genetic distances (0.000–0.011) observed samples between two distinct drainage systems in Manipur and Mizoram, northeastern India. The observed pattern of haplotype divergence in G. manipurensis may reflect the historical or seasonal hydrological connectivity among the western-slope drainages of the Chin Hills, with the subsequent geographic isolation potentially contributing to the emergence of distinct genetic lineages. Nevertheless, the extent and evolutionary significance of this differentiation remain uncertain and warrant further investigation through expanded geographic sampling and the incorporation of additional molecular data. Collectively, these findings provide in-depth insights into the mitogenomic architecture, comparative gene arrangements, phylogenetic patterns, and matrilineal evolutionary history of G. manipurensis and other congeners, thereby improving our understanding of the systematics and genetic diversity of this important cyprinid fish lineage. Full article

Mitochondrial DNA (mtDNA) analysis is a fundamental tool in forensic genetics, particularly when biological samples exhibit severe degradation or low nuclear DNA content. Its unique biological characteristics, such as a high copy number per cell, strict matrilineal inheritance, and lack of recombination, enable human identification and reconstruction of maternal lineages in complex contexts, including disaster victim identification, historical cases, and missing persons investigations. This narrative review examines contemporary methodological approaches for investigating the human mitogenome. We discuss recent advancements in extraction and enrichment techniques, emphasizing their efficacy in reducing the interference of nuclear mitochondrial DNA sequences (NUMTs) and enhancing the recovery of informative fragments. Moreover, the shift from traditional Sanger sequencing to Massive Parallel Sequencing (MPS) is examined, as MPS has markedly enhanced the sensitivity and capability of contemporary methods to detect low-frequency heteroplasmies. Additionally, the advent of Third-Generation Sequencing (TGS), exemplified by nanopore platforms, is evaluated, which facilitates the reading of full-length native molecules without the biases introduced by PCR amplification. Despite the interpretive challenges posed by heteroplasmy, contamination, and limitations in population databases, ongoing methodological advances in mitochondrial DNA analysis continue to strengthen its reliability and expand its potential in forensic genetics. Full article

This paper explores the intersection of embodied trauma, resilience, and healing as represented in contemporary art, focusing on a case study analysis of the autoethnographic practice as a reflexive methodology that integrates personal lived experience with cultural, political, and artistic analysis of the works of Zlatar. Central to this study is examining the notion of rematriation, which calls for the reclamation of women’s histories and the restoration of knowledge passed down through generations. Through a series of her paintings, including works from her series A Serbian Renaissance, Refuge For the Oppressed Body, and The Minotaur Came and I Surrendered, Zlatar interrogates the transmission of trauma across generations of women, from Balkan origins, focusing on issues such as gender-based violence, displacement, and identity formation. These works challenge dominant narratives by centring women’s experiences not through externalized indicators or representations of healing, but mediating how mind–body relationships have dialogue, and her art employs this concept as spaces for memory, survival, and meaning-making. Drawing on feminist philosophy, artwork analysis and trauma studies, this paper situates Zlatar’s art to address historical inequities in women’s healing and the ongoing struggle for women’s agency and safety in contemporary society. Full article

Sleeping-site selection is a critical decision-making process in animals, influenced by evolutionary pressures. However, the key factors controlling this choice under group demography, and how these vary seasonally, remain poorly understood. This study investigated the selection of arboreal versus terrestrial sleeping sites and the underlying decision-making processes in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China, across mating (July–January) and non-mating (February–April) seasons. Generally, Tibetan macaques slept arboreally during mating season (July–September), switched to terrestrial sites afterward (October–March), and returned to trees in the following April. As for the decision-making, females consistently played a central role, initiating collective movements to arboreal sites more frequently and attracting more followers during the mating season, and joining the collective movements earlier across all seasons. Decision-making rules also varied seasonally. Females and middle-aged/older individuals mainly initiated movements to arboreal sites during the mating season, whereas terrestrial movements were led primarily by older individuals, with high social centrality attracting more followers. In the non-mating season, no specific social traits predicted initiators across sleeping sites, though females consistently attracted more followers and joined movements earlier. In terrestrial movements specifically, older individuals joined later, whereas highly socially central individuals joined earlier. Our research reveals that the sleeping-site selection decisions of Tibetan macaques are influenced by their matrilineal group structure. This study provides insights into the ecological adaptability of primates, demonstrating how dynamic decision-making supports survival in seasonal environments among social animals. Full article

Leopards (Panthera pardus) are considered solitary carnivores, but recent research reveals a more complex lifestyle that incorporates kin selection, hidden social structures, and behavioral innovation and plasticity. This paper combines theoretical advancements in kin selection with empirical findings from the peri-urban Jhalana Forest Reserve in Jaipur, India. Our research demonstrates that kin-tolerant spatial organization, maternal investment, temporal avoidance strategies, and adaptive responses to human-induced pressures form the foundation of leopard ecology in Jhalana. Female philopatry leads to the formation of matrilineal clusters, and maternal strategies play a crucial role in cub survival, with a cumulative two-year survival rate estimated at 61.8%. Emotional behaviors, such as grief-like responses to the loss of cubs, further challenge the notion that leopards are purely solitary animals. These findings have significant implications for evolutionary theory, conservation management, and human–wildlife coexistence. Jhalana serves as a model system where solitude and social behavior intersect, redefining our understanding of leopard ecology and guiding conservation efforts in human-dominated landscapes. Full article

Background/Objectives: Arctic foxes (Vulpes lagopus) exemplify the vulnerability of Arctic species to global warming and anthropogenic impacts, including habitat loss, interspecific competition with temperate species, pollution (chemical and biological), and declining prey abundance. Despite their ecological importance, the evolutionary and demographic history of the species is still incompletely understood, and the colonization history of isolated island populations, such as the one on Iceland, remains unresolved. Methods: We analyzed 80 mitochondrial genomes from across the Holarctic, including 22 Icelandic individuals. We combined phylogenetic reconstruction, coalescence-dating, haplotype network analysis, and diversity metrics to infer matrilineal relationships and colonization history. Results: Seven distinct haplogroups (Hg.1–Hg.7) were identified, which diverged ≥65 thousand years ago (kya). Two haplogroups were broadly distributed across Fennoscandia, Russia, Iceland, and Canada, while others were region-specific: two in eastern Russia (respectively diverging ~171 kya and ~89 kya), one in central Russia (~66 kya), and two in Iceland (~95 kya and ~66 kya). Three haplogroups were detected in Iceland, and at least four unrelated founding females are required to explain the current matrilineal diversity. One haplogroup contained sufficient representatives for molecular dating, yielding a minimum colonization age of ~5600 years, assuming in situ diversification. Observed matrilineal diversity in Iceland does not uniquely identify a single geographic source. Conclusions: Arctic foxes’ distribution and diversity reflect repeated cycles of isolation and expansion as circumpolar environments shifted. Broader sampling across the Nearctic is critical to clarify the timing, sources, and routes of Iceland’s colonization, as Nearctic sampling was limited to a single Canadian mitogenome. Full article

Despite its ecological and economic importance, Hampala macrolepidota (Cyprinidae: Smiliogastrinae) remains taxonomically debated, having undergone historical reclassifications across multiple taxonomic ranks. These challenges highlight the urgent need for integrative genomic analyses to resolve its phylogeny and assess genome-wide diversity, establishing a baseline for effective management and conservation. In this study, the newly assembled mitogenome of H. macrolepidota from within its native range in Lake Dibawah, West Sumatra, Indonesia, was sequenced. The mitogenome spanned 17,104 bp, encoded 37 genes and a control region, and exhibited a nucleotide composition biased toward adenine and thymine. The protein-coding genes (PCGs) predominantly utilized ATG as the initiation codon and showed a higher proportion of hydrophobic compared to hydrophilic amino acids. The nonsynonymous (Ka) and synonymous (Ks) substitution ratios were below ‘1’, which indicates negative selection on most of the PCGs within Hampala and other Smiliogastrinae species. Mitogenome-wide analysis revealed overall high intraspecific genetic diversity (≥2.7%) in the native Indonesian population compared to mainland populations in Southeast Asia. The Bayesian and maximum-likelihood phylogenetic analyses elucidated matrilineal evolutionary relationships within the subfamily Smiliogastrinae, with the Hampala species forming a monophyletic cluster. The present mitogenome-based phylogenetic topologies also supported the taxonomic placement of several species in the revised classification, which previously were classified under the genera Puntius and Barbus, respectively. Additionally, the investigation of partial mitochondrial COI and Cytb genes further elucidated the population genetic structure of H. macrolepidota across Southeast and East Asia. The observed genetic divergence (0–4.2% in COI and 0–4.5% in Cytb), together with well-resolved phylogenetic clustering and the presence of both shared and distinct haplotypes among Indonesian samples, provides strong evidence for long-term population isolation and local adaptation. These patterns are most plausibly driven by historical hydrological dynamics, paleo-drainage connectivity, and persistent geographic barriers that have structured population divergence over time. In addition, this study emphasizes the need to generate mitogenomes of seven additional Hampala species from Southeast Asia to better understand their evolutionary patterns. Further, broader sampling of wild H. macrolepidota populations across their biogeographical range will be essential to strengthen understanding of their genetic diversity and guide effective conservation strategies. Full article

While the legal framework in Mozambique in principle provides equal rights to land for women and men, its underlying assumptions imply that customary tenure is patrilineal, that women get access to land through their relationships with men, while men in practice own and control land. This article focuses on matrilineal land institutions in Makhuwa communities in northern Mozambique. It argues that local matrilineal institutions have provided women with transferable rights to land, while men get access to land in various ways within the matrilineal institutional framework. Based on the Land Law of 1997, the Mozambican government in 2015 launched a large-scale land tenure formalisation programme, Terra Segura (“Secure Land”), with World Bank funding. The Mozambican Land Law recognises local community rights to customary land, while Land Law Regulations define the requirements for both community and individual formalisation of such rights. Field data collected in Makhuwa communities, where individual titling was carried out in the period 2019–2023, indicate that both women and men received titles. But what is secured through these individual titles? The article discusses to what extent formalised “secure land tenure” for individuals can weaken women’s land rights and traditional rights to subsistence—provided by matrilineal land institutions over time, across generations. Full article

Butidae is a family of teleost fishes with diverse morphological and ecological adaptations, including the marbled goby (Oxyeleotris marmorata), a large species of high economic value in Southeast and East Asia. The previous mitogenomic studies on cultured populations of O. marmorata from non-native habitats have provided limited insights into genetic divergence, structural variation, and evolutionary relationships. Hence, this study presented the complete mitochondrial genome of O. marmorata from its native habitat in Indonesia, providing structural characterization, assessment of genetic diversity, and matrilineal phylogenetic analysis. The circular mitogenome was 16,525 bp, comprising 37 genes and a non-coding control region (CR). The gene organization and strand distribution were conserved among Oxyeleotris species, with 28 genes on the heavy strand and nine on the light strand, and a pronounced A+T compositional bias. The comparative analyses of O. marmorata (from both native and cultured habitats) and Oxyeleotris lineolata mitogenomes revealed minor variations in intergenic spacers, gene overlaps, protein-coding gene (PCGs) lengths, and codon usage patterns. Conversely, the nonsynonymous and synonymous substitution ratios observed in species of the family Butidae and its closest related family (Eleotridae) indicate strong purifying selection in the present dataset. Notably, the ATG was the predominant start codon, whereas the COI gene utilized GTG, and amino acid composition analysis demonstrated high frequencies of arginine, leucine, and serine. Most transfer RNAs retained the canonical cloverleaf secondary structure except for trnS1, which lacked a functional dihydrouridine arm, whereas the CR contained four conserved sequence blocks with variable nucleotide motifs and no detectable tandem repeats. The haplotype analysis of native (Indonesia) and introduced populations (China) highlighted three haplotypes with high diversity (Hd = 1.0000) and substantial nucleotide variation (π = 0.6667). The genetic divergence across 13 PCGs was gene-specific, with COI and ND5 showing the highest variation, while ND4L and ATP8 were highly conserved. The phylogenetic analyses based on concatenated 13 PCGs using both Bayesian Inference and Maximum Likelihood methods revealed that Oxyeleotris forms a monophyletic clade and is closely related to Bostrychus sinensis. In addition, the broader phylogenetic framework inferred the matrilineal relationships within the family Butidae and its closest related family, Eleotridae. This study also recommends expanding analyses to include the mitogenomes of the remaining 17 Oxyeleotris species, together with comprehensive genomic data, to further elucidate their genetic architecture, evolutionary history, and ecological adaptability across diverse aquatic ecosystems. Full article

The intracellular retention of misfolded extracellular matrix proteins is a common disease mechanism in various rare skeletal diseases. This discovery has driven the study of ER stress and the unfolded protein response (UPR) as a promising therapeutic target in several skeletal dysplasias. In the case of COL10A1 mutations, targeting the UPR resulted in a clinical trial of the repurposed drug carbamazepine; however, for other closely related skeletal disorders, treatment with carbamazepine was ineffective, indicating the need for suitable markers for in vitro screenings of potential drug treatments. Mutations in cartilage oligomeric matrix protein (COMP), a cartilage structural protein, cause both multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH); together referred to as the COMPopathies, which result from the intracellular retention of mutant COMP to varying degrees. In contrast to other closely related skeletal disorders, caused by mutations in cartilage structural proteins, the involvement of the UPR is less clear, and so far, no common COMPopathy marker has been identified. Here, using cell models of COMPopathies, we identified MMP9 upregulation as a common feature of six pathogenic COMP variants that do not induce a prominent UPR. We further show that the archetypal p.V194D matrilin-3 MED variant (which causes MED) does not induce MMP9 expression, suggesting that MMP9 upregulation could serve as a specific marker of COMPopathies in vitro. Full article

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are rare, autosomal dominant skeletal dysplasias characterised by disproportionate short stature, joint deformities, and early-onset osteoarthritis. These conditions result from mutations in key cartilage extracellular matrix (ECM) components, including cartilage oligomeric matrix protein (COMP), matrilin-3, and type IX collagen. Although genetically and clinically heterogeneous, PSACH and MED share convergent pathogenic mechanisms. Misfolded mutant ECM proteins are retained within the endoplasmic reticulum (ER) of growth plate chondrocytes, triggering chronic ER stress and impairing chondrocyte proliferation, differentiation, and survival. Moreover, some of the mutant protein is secreted and incorporated into the matrix, leading to altered collagen fibrillogenesis, disrupted proteoglycan distribution, and compromised biomechanical integrity. These alterations extend beyond cartilage, impacting tendons, ligaments, and muscle–tendon junctions, contributing to joint laxity, impaired force transmission, and mild myopathy. This review discusses the structural and functional consequences of ECM disorganisation in PSACH and MED, highlighting its central role in disease progression and emphasising the importance of considering ECM abnormalities when developing therapeutic strategies for rare short stature-associated skeletal disorders. Full article

Background/Objectives: In this study, we conducted molecular identification of R.microplus and explored the genetic diversity of R. microplus for the first time in Mizoram, a Northeastern Hill (NEH) state of India bordering Myanmar. Methods: To assess genetic variation and evolutionary relationships, we employed phylogenetic analyses, genetic divergence metrics, and haplotype network construction based on mitochondrial (COX1 and 16S rDNA) and nuclear (ITS-2 and 18S rDNA) markers. Additionally, multivariate Principal Coordinate Analysis (PCoA) was used to visualize genetic differentiation among R. microplus populations. Results: Our analyses indicated that populations of R. microplus sensu lato from India, Bangladesh, and Pakistan form a closely related matrilineal lineage distinct from R. microplus sensu stricto, clustering within clade C of the COX1-based phylogeny. Globally, 24 COX1 haplotypes were recovered, with 1 haplotype identified in India. The Mizoram population exhibited a single 16S rDNA haplotype; however, intraspecific divergence was evident across India, with seven matrilineal haplotypes detected and nineteen globally. Further, five haplotypes were identified within R. microplus using the ITS-2 marker, while five haplotypes were observed within the Rhipicephalus genus using the 18S rDNA marker. Moreover, this study revealed the presence of Coxiella-like endosymbionts in 95% of the tick specimens analyzed. Conclusions: This study fills a critical knowledge gap by providing the first molecular documentation of tick diversity in Mizoram, a strategic region along the Indo–Myanmar border, and offers novel insights into the phylogeography and symbiotic associations of R. microplus and related tick taxa. Full article