Search Results (2,170)

Background: Botulinum toxin type A (BoNT/A) is widely used in both clinical and aesthetic settings to induce temporary neuromuscular paralysis by inhibiting acetylcholine release. Although generally regarded as safe and effective, complications such as iatrogenic ptosis or facial asymmetry may occur and persist for several weeks or even months, with no standardized method currently available to accelerate recovery. Objective: This article explores the hypothesis that photobiomodulation (PBM)—a non-invasive modality recognized for its neuroregenerative potential—may facilitate the reversal of BoNT/A-induced neuromuscular blockade. Discussion: PBM enhances mitochondrial activity by stimulating cytochrome c oxidase in nerve and muscle tissues, thereby increasing ATP production and modulating intracellular signaling pathways associated with neuroplasticity, cell survival, and synaptogenesis. Preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects. While controlled clinical trials for this specific application are currently lacking, anecdotal clinical reports suggest that PBM may accelerate functional recovery in cases of BoNT/A-related complications. Conclusions: Although this approach has not yet been tested in clinical trials, we propose that photobiomodulation may hypothetically serve as a supportive strategy to promote neuromuscular recovery in patients experiencing adverse effects from BoNT/A. This hypothesis is grounded in robust preclinical evidence but requires validation through translational and clinical research. Full article

Caenogastropoda is a highly speciose and ecologically diverse subclass of Gastropoda but its higher order classification remains unclear, especially within its largest constituent group, Hypsogastropoda. Two nominal taxa encompassing most of the great diversity of Hypsogastropoda are in current widespread use: one is Latrogastropoda, which has been repeatedly redefined resulting in changes to the second, Littorinimorpha, which is generally not supposed to be monophyletic. We examined the utility of these divisions by assembling single-gene data sets of nuclear 28S ribosomal RNA (28S rRNA) and mitochondrial 16S ribosomal RNA (16S rRNA) and cytochrome c oxidase subunit I from many genera. Capuloidea was consistently found with strong support within Latrogastropoda, so this taxon is redefined here to include that superfamily. The analyses also suggested the redefinition of some superfamilies within Littorinimorpha, particularly for the clade comprising Truncatelloidea, Vanikoroidea and Rissooidea, and the Littorinoidea. Littorinimorpha was monophyletic (albeit lacking strong support) in the combined analysis of 28S rRNA and 16S rRNA and was resolved as the sister group of Latrogastropoda which was also monophyletic, with bootstrap support of 66%. Littorinimorpha was not monophyletic in other analyses. In these, the sister group of Latrogastropoda comprised clades of multiple littorinimorph superfamilies but these relationships were also not strongly supported. Full article

Of breast cancers, the triple-negative subtype (TNBC) is characterized by aggressive behavior, poor prognosis and limited treatment options due to its high molecular heterogeneity. Since insufficient programmed cell death response is a major hallmark of cancer, here we searched for apoptosis-related biomarkers of prognostic potential in TNBC. The expression of the pro-apoptotic caspase 8, cytochrome c, caspase 3, the anti-apoptotic BCL2 and the caspase-independent mediator, apoptosis-inducing factor-1 (AIF1; gene AIFM1) was tested in TNBC both in silico at transcript and protein level using KM-Plotter, and in situ in our clinical TNBC cohort of 103 cases using immunohistochemistry. Expression data were correlated with overall survival (OS), recurrence-free survival (RFS) and distant metastasis-free survival (DMFS). We found that elevated expression of the executioner apoptotic factors AIF1 and caspase 3, and of BCL2, grants significant OS advantage within TNBC, both at the mRNA and protein level, particularly for chemotherapy-treated vs untreated patients. The dominantly cytoplasmic localization of AIF1 and cleaved-caspase 3 proteins in primary TNBC suggests that chemotherapy may recruit them from the cytoplasmic/mitochondrial stocks to contribute to improved patient survival in proportion to their expression. Our results suggest that testing for the expression of AIF1, caspase 3 and BCL2 may identify partly overlapping TNBC subgroups with favorable prognosis, warranting further research into the potential relevance of apoptosis-targeting treatment strategies. Full article

The electrodynamics of current provide much of our technology, from telegraphs to the wired infrastructure powering the circuits of our electronic technology. Current flow is analyzed by its own rules that involve the Maxwell Ampere law and magnetism. Electrostatics does not involve magnetism, and so current flow and electrodynamics cannot be derived from electrostatics. Practical considerations also prevent current flow from being analyzed one charge at a time. There are too many charges, and far too many interactions to allow computation. Current flow is essential in biology. Currents are carried by electrons in mitochondria in an electron transport chain. Currents are carried by ions in nerve and muscle cells. Currents everywhere follow the rules of current flow: Kirchhoff’s current law and its generalizations. The importance of electron and proton flows in generating ATP was discovered long ago but they were not analyzed as electrical currents. The flow of protons and transport of electrons form circuits that must be analyzed by Kirchhoff’s law. A chemiosmotic theory that ignores the laws of current flow is incorrect physics. Circuit analysis is easily applied to short systems like mitochondria that have just one internal electrical potential in the form of the Hodgkin Huxley Katz (HHK) equation. The HHK equation combined with classical descriptions of chemical reactions forms a computable model of cytochrome c oxidase, part of the electron transport chain. The proton motive force is included as just one of the components of the total electrochemical potential. Circuit analysis includes its role just as it includes the role of any other ionic current. Current laws are now needed to analyze the flow of electrons and protons, as they generate ATP in mitochondria and chloroplasts. Chemiosmotic theory must be replaced by an electro-osmotic theory of ATP production that conforms to the Maxwell Ampere equation of electrodynamics while including proton movement and the proton motive force. Full article

Fruit size is an important agronomic trait affecting the yield and commercial value of melon and a key trait selected for during domestication. In this study, two respective melon accessions (large-fruited M202008 and small-fruited M202009) were crossed, and developed biparental mapping populations of the F₂ generation (160 and 382 plants) were checked across two subsequent experimental years (2023 and 2024). The phenotypic characterization and genetic inheritance analysis showed that melon fruit size is modulated by quantitative genetics. Bulked segregant sequencing analysis (BSA-seq) identified a stable and effective quantitative trait locus (QTL, named Cmfs) controlling fruit size, localized to a 3.75 Mb region on chromosome 9. To better delineate the main-effect Cmfs locus, co-dominant polymorphic molecular markers were developed in this genetic interval, and genotyping was performed within the F₂ mapping populations grown across two years. QTL analysis of the phenotypic and genotypic datasets delimited the major-effect Cmfs locus interval for fruit length [2023: logarithm of odds (LOD) value = 6.16, 16.20% phenotypic variation explained (PVE); 2024: LOD = 5.44, 6.35% PVE] and fruit diameter (2023: LOD value = 5.48, 14.59% PVE; 2024: LOD = 6.22, 7.22% PVE) to 1.88 and 2.20 Mb intervals, respectively. The annotation analysis across the melon genome and comparison of resequencing data from the two parental lines led to the preliminary identification of MELO3C021600.1 (annotated as cytochrome P450 724B1) as a candidate gene related to melon fruit size. These results provide a better understanding for further fine mapping and functional gene analysis related to melon fruit size. Full article

Large-conductance, voltage- and calcium-activated potassium (BK) channels are crucial regulators of cellular excitability, influenced by various signaling molecules, including heme. The BK channel contains a heme-sensitive motif located at the sequence ⁶¹²CKACH⁶¹⁶, which is a conserved heme regulatory motif (HRM) found in the cytochrome c protein family. This motif is situated within a linker region of approximately 120 residues that connect the RCK1 and RCK2 domains, and it also includes terminal α-helices similar to those found in cytochrome c family proteins. However, much of this region has yet to be structurally defined. We conducted a sequence alignment of the BK linker region with mitochondrial cytochrome c and cytochrome c domains from various hemoproteins to better understand this functionally significant region. In addition to the HRM motif, we discovered that important structural and functional elements of cytochrome c proteins are conserved in the BK RCK1-RCK2 linker. Firstly, the part of the BK region that is resolved in available atomic structures shows similarities in secondary structural elements with cytochrome c domain proteins. Secondly, the Met80 residue in cytochrome c domains, which acts as the second axial ligand to the heme iron, aligns with the BK channel. Beyond its role in electron shuttling, cytochrome c domains exhibit various catalytic properties, including peroxidase activity—specifically, the oxidation of suitable substrates using peroxides. Our findings reveal that the linker region endows human BK channels with peroxidase activity, showing an apparent H₂O₂ affinity approximately 40-fold greater than that of mitochondrial cytochrome c under baseline conditions. This peroxidase activity was reduced when substitutions were made at ⁶¹²CKACH⁶¹⁶ and other relevant sites. These results indicate that the BK channel possesses a novel module similar to the cytochrome c domains of hemoproteins, which may give rise to unique physiological functions for these widespread ion channels. Full article

Enhancing quality traits is a primary objective in silage maize breeding programs. The use of genome-wide association studies (GWAS) for quality traits, in combination with the integration of genetic resources, presents an opportunity to identify crucial genomic regions and candidate genes influencing silage maize quality. In this study, a GWAS was conducted on 580 inbred lines of silage maize, and a meta-analysis was performed on 477 quantitative trait loci (QTLs) from 34 studies. The analysis identified 27 significant single nucleotide polymorphisms (SNPs) and 87 consensus QTLs (cQTLs), with 7 cQTLs associated with multiple quality traits. By integrating the SNPs identified through association mapping, one SNP was found to overlap with the cQTL interval related to crude protein, neutral detergent fiber, and starch content. Furthermore, enrichment analysis predicted 300 and 5669 candidate genes through GWAS and meta-analysis, respectively, highlighting pathways such as cellular metabolism, the biosynthesis of secondary metabolites, ribosome function, carbon metabolism, protein processing in the endoplasmic reticulum, and amino acid biosynthesis. The examination of 13 candidate genes from three co-located regions revealed Zm00001d050977 as a cytochrome P450 family gene, while the other 2 genes primarily encode proteins involved in stress responses and other biological pathways. In conclusion, this research presents a methodology combining GWAS and meta-analysis to identify genomic regions and potential genes influencing quality traits in silage maize. These findings serve as a foundation for the identification of significant QTLs and candidate genes crucial for improving silage maize quality. Full article

In this study, the association between Neosilba batesi (Diptera: Lonchaeidae) and avocado fruits (Persea americana L.) was investigated. Fruits showing signs of rot and infested with Diptera larvae were collected from commercial orchards in the states of Michoacán and Jalisco, Mexico. N. batesi was identified in association with fruits from both trees and the ground at all sampling sites. Furthermore, a phylogenetic analysis based on the mitochondrial cytochrome c oxidase subunit I (COI) gene supported the morphological identification, showing >99% identity with records from Veracruz, and revealed distinct genetic lineages within the Neosilba genus. In a study within one Michoacán orchard, infested tree-borne fruits averaged 5.40 cm in length and 3.90 cm in width, with a mean of 9.61 larvae emerging per fruit. Females were observed to lay eggs in openings between the pedicel and the fruit, never piercing the exocarp. In contrast, on fallen fruit, they utilized existing wounds with exposed pulp. Infested avocados exhibit characteristic spots indicating the presence of internal larvae and generally detach from the tree. Larvae can feed on avocados in various stages of decomposition and may either emerge through wounds or pupate within the fruit. These findings support the opportunistic and saprophagous behavior associated with this fly species. Full article

The aim of this study was to determine whether a low dose of zearalenone (ZEN) affects the mRNA expression of the CYP1A1 (P450 cytochrome) and GSTπ1 (glutathione S-transferase) genes in the large intestine of pre-pubertal gilts. Materials: Control (C) group gilts (n = 18) received a placebo. Experimental (E) group gilts (n = 18) were orally administered 40 μg ZEN/kg body weight (BW) each day before morning feeding for 42 days. Three animals from each group were sacrificed each week of the study. Tissue samples were collected from the medial parts of the ascending colon and the descending colon on six dates. Results: Zearalenone concentrations were multiple times higher in the last three weeks of exposure, and ZEN metabolites were not detected. In phase I, CYP1A1 mRNA expression in the ascending colon was suppressed in the final three weeks of exposure, which substantially increased the ZEN concentration in the descending colon. In phase II, ZEN levels were high in the descending colon due to CYP1A1 suppression in the ascending colon. Consequently, the phase II detoxification processes could not take place due to the absence of a substrate. Conclusion: This study demonstrated that low-dose ZEN mycotoxicosis disrupts the expression of the CYP1A1 and GSTπ1 genes, which co-participate in the enzymatic biotransformation of ZEN in both examined sections of the large intestine. The above could have contributed to increased ZEN accumulation in the mucosa of the descending colon in the last three weeks of exposure. Full article

Maternal obesity programs the fetus for increased risk of chronic disease development in early life and adulthood. We hypothesized that maternal nutrient excess leads to fetal inflammation and impairs offspring skeletal muscle mitochondrial biogenesis in non-human primates. At least 12 months before pregnancy, female baboons were fed a normal chow (CTR, 12% energy fat) or a maternal nutrient excess (MNE, 45% energy fat, and ad libitum fructose sodas) diet, with the latter to induce obesity. After 165 days of gestation (0.9 G), offspring baboons were delivered by cesarean section, and the soleus muscle was collected (CTR n = 16, MNE n = 5). At conception, MNE mothers presented increased body fat and weighed more than controls. The soleus muscle of MNE fetuses exhibited increased levels of stress signaling associated with inflammation (TLR4, TNFα, NF-kB p65, and p38), concomitant with reduced expression of key regulators of mitochondrial biogenesis, including PGC1α, both at the protein and transcript levels, as well as downregulation of PPARGC1B, PPARA, PPARB, CREB1, NOS3, SIRT1, SIRT3. Decreased transcript levels of NRF1 were observed alongside diminished mitochondrial DNA copy number, mitochondrial fusion elements (MFN1, MFN2), cytochrome C protein levels, and cytochrome C oxidase subunits I and II transcripts (cox1 and cox2). MNE coupled to MO-induced stress signaling in fetal baboon soleus muscle is associated with impaired mitochondrial biogenesis and lower mitochondrial content, resembling the changes observed in metabolic dysfunctions, such as diabetes. The observed fetal alterations may have important implications for postnatal development and metabolism, potentially increasing the risk of early-onset metabolic disorders and other non-communicable diseases. Full article

Nitric oxide (NO) has a dual effect on mitochondria. Incubating liver mitochondria with NO improves oxidative phosphorylation (OXPHOS) efficiency by decreasing state 4 respiration more than ATP synthesis and preventing mitochondrial permeability transition pore (mPTP) opening. We evaluated the effect of L-arginine (L-arg), an NO donor, on isolated liver mitochondrial respiration and mPTP in sepsis. Male mice were subjected to cecal ligation and perforation (CLP) with saline resuscitation or sham. After 8, 24, and 48 h, with and without L-arg, we measured isolated liver mitochondrial respiration and cytochrome c oxidase (COX) activity using polarographic methods and calcium retention capacity (CRC) to assess the mPTP and NO metabolites via the Griess reaction. Mitochondrial NO synthase (mtNOS) was identified by Western blot. CLP decreased state 3 respiration at 24 and 48 h, decreased COX activity at 8, 24, and 48 h, and increased state 4 respiration and decreased the respiratory control ratio (RCR) and CRC at 48 h. L-arg increased NO levels at 8 h, decreased state 4 respiration more than state 3 respiration (−39% versus −12%) at 48 h, decreased the CRC in the CLP groups at 24 and 48 h, but did not improve RCR. Our data suggests that L-arg does not restore liver mitochondrial OXPHOS efficiency or prevent mPTP opening in the late or recovery phases of sepsis. Full article

Castor fiber birulai is a subspecies of the Eurasian beaver that has a relatively small population size compared to other Castor subspecies. There is limited genetic research on this subspecies. In this study, mitochondrial cytochrome b (Cytb) and D-loop sequences were analysed in genetic samples obtained from 19 individuals residing in the Buergen River Basin, Xinjiang, China. The Cytb region presented a single haplotype, whereas three haplotypes were identified in the D-loop region. The genetic diversity within the Chinese population was low (D-loop Hd = 0.444; Pi = 0.0043), markedly lower than that observed in other geographical populations of C. fiber. Phylogenetic reconstructions and haplotype network analyses revealed substantial genetic differentiation between C. f. birulai and other Eurasian lineages (Fst > 0.95), supporting the status of C. f. birulai as a distinct evolutionary lineage. Although the genetic distance between the Chinese and Mongolian populations was relatively small (distance = 0.00269), significant genetic differentiation was detected (Fst = 0.67055), indicating that anthropogenic disturbances—such as hydraulic infrastructure and fencing along the cross-border Bulgan River—may have impeded gene flow and dispersal. Demographic analyses provided no evidence of recent population expansion (Fu’s Fs = 0.19152), suggesting a demographically stable population. In subsequent studies, we recommend increasing nuclear gene data to verify whether the C. f. birulai population meets the criteria for Evolutionarily Significant Unit classification, and strengthening cross-border protection and cooperation between China and Mongolia. Full article

Background: The treatment landscape for multiple myeloma (MM) has significantly evolved in recent decades with novel therapies like proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. However, MM remains incurable, necessitating new pharmacological strategies. Mitotic kinases, such as Aurora proteins, have emerged as potential targets. Selective inhibitors of Aurora A and B,- alisertib (MLN8237) and barasertib (AZD1152), respectively, have shown anti-myeloma activity in preclinical studies, with alisertib demonstrating modest efficacy in early clinical trials. Methods and Results: This study investigated the mechanisms of action of alisertib and barasertib and their combination with antitumor agents in a panel of five MM cells lines. Both drugs induced cell cycle arrest phase and abnormal nuclear morphologies. Alisertib caused prolonged mitotic arrest, whereas barasertib induced transient arrest, both resulting in the activation of mitotic catastrophe. These findings revealed three potential outcomes: cell death, senescence, or polyploidy. High mitochondrial reactive oxygen species (mROS) were identified as possible drivers of cell death. Caspase inhibition reduced caspase-3 activation but did not prevent cell death. Interestingly, alisertib at low doses remained toxic to Bax/Bak^DKO cells, although mitochondrial potential disruption and cytochrome c release were observed. Sequential combinations of high-dose Aurora kinase inhibitors with BH3-mimetics, and in specific cases with panobinostat, showed a synergistic effect. Conversely, the simultaneous combination of alisertib and barasertib showed mostly antagonistic effects. Conclusions: Alisertib and barasertib emerge as potential in vitro candidates against MM, although further studies are needed to validate their efficacy and to find the best combinations with other molecules. Full article

A periplasmic D-malate:cytochrome c oxidoreductase (DMCO) was identified in Ectopseudomonas oleovorans CECT5344, utilizing 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl tetrazolium chloride (INT) as an artificial electron acceptor. The assay was adapted for a spectrophotometric or native polyacrylamide gel electrophoresis (PAGE) analysis. The DMCO-encoding gene (BN5_4044) was cloned and expressed in Escherichia coli, enabling a partial purification and biochemical characterization. In addition to D-malate, the enzyme oxidizes D-2-hydroxyglutarate and, to a lesser extent, D-lactate, with cytochrome c also serving as an electron acceptor. DMCO requires Zn²⁺ for activity and exists as a dimer, as determined by gel filtration. The in vitro reconstitution of the electron transfer from D-malate to oxygen was achieved using spheroplasts, enriched periplasmic fractions, and cytochrome c. This extracytoplasmic respiration, unique among homologs of this protein, may eliminate the need for a dedicated inner membrane transporter, thereby avoiding potential upstream respiratory bottlenecks. In the context of bioremediation, and particularly regarding the cyanide metabolism, this D-malate oxidation to oxaloacetate facilitates detoxification by forming the corresponding cyanohydrin, which can be subsequently assimilated for growth. Full article

The green octopus, Octopus hubbsorum, is a merobenthic species that inhabits warm-temperate waters in the eastern Pacific. However, its similarity to some morphological characteristics of and its slight genetic divergence from Octopus mimus has led to the proposal that both species are conspecific. The objective of this study was the morphological and molecular identification of eggs and paralarvae of the green octopus, O. hubbsorum, to provide information contributing to clarifying its taxonomy and relationship with O. mimus. The results obtained show that although O. hubbsorum has similarities with O. mimus in terms of egg size, chromatophore pattern, number of suckers, and presence of Kölliker’s organs, the O. hubbsorum paralarvae observed in this study are smaller (1.6 mm) and have a thin layer of loose skin, not described for O. mimus. Likewise, the morphology of the beak, radula, and suckers of O. hubbsorum is described for the first time and there are no studies of these structures for O. mimus. The phylogenetic analysis (mitochondrial cytochrome C oxidase subunit I and III genes) showed that both species form a monophyletic clade but belong to separate subclades. In conclusion, although the slight genetic divergence between these two species suggests conspecificity, their disjoint geographic distribution (O. hubbsorum is found in warm-temperate waters and O. mimus in cold-temperate waters) suggests the hypothesis of being two separate species with a close phylogenetic relationship. However, further research (morphological and population analyses) is required to solve taxonomic uncertainty. Full article