Search Results (149)

The Xenopus oocyte has long served as a versatile and powerful model for dissecting the molecular underpinnings of reproductive and developmental processes. Its large size, manipulability, and well-characterized cell cycle states have enabled generations of researchers to illuminate key aspects of oocyte maturation, fertilization, and early embryogenesis. This review provides an integrated overview of the cellular and molecular events that define the Xenopus oocyte’s transition from meiotic arrest to embryonic activation—or alternatively, to programmed demise if fertilization fails. We begin by exploring the architectural and biochemical landscape of the oocyte, including polarity, cytoskeletal organization, and nuclear dynamics. The regulatory networks governing meiotic resumption are then examined, with a focus on MPF (Cdk1/Cyclin B), MAPK cascades, and translational control via CPEB-mediated cytoplasmic polyadenylation. Fertilization is highlighted as a calcium-dependent trigger for oocyte activation. During fertilization in vertebrates, sperm-delivered phospholipase C zeta (PLCζ) is a key activator of Ca²⁺ signaling in mammals. In contrast, amphibian species such as Xenopus lack a PLCZ1 ortholog and instead appear to rely on alternative protease-mediated signaling mechanisms, including the uroplakin III–Src tyrosine kinase pathway and matrix metalloproteinase (MMP)-2 activity, to achieve egg activation. The review also addresses the molecular fate of unfertilized eggs, comparing apoptotic and necrotic mechanisms and their relevance to reproductive health. Finally, we discuss recent innovations in Xenopus-based technologies such as mRNA microinjection, genome editing, and in vitro ovulation systems, which are opening new avenues in developmental biology and translational medicine. By integrating classic findings with emerging frontiers, this review underscores the continued value of the Xenopus model in elucidating the fundamental processes of life’s origin. We conclude with perspectives on unresolved questions and future directions in oocyte and early embryonic research. Full article

In the Mediterranean region, the persimmon cultivar ‘Rojo Brillante’ may experience up to four waves of fruit drop. The first is a physiological event during fruit set that is common in woody species, while the subsequent waves are induced by rising temperatures and prolonged summer water stress. These summer drops represent the main limiting factor, leading to yield losses of up to 90%. Organ abscission is a complex process regulated by genetic, hormonal, nutritional, and environmental factors. We hypothesise that calcium (Ca) plays a protective role in the abscission zone (AZ) by inhibiting cell wall-degrading enzymes such as polygalacturonase (PG) and pectin methylesterases (PMEs). Calcium applications every 15 days from anthesis onwards significantly reduced fruit drop. Treatments preserved polar auxin transport—through DkPIN1 expression—and inhibited stage C of the abscission process, decreasing the relative expression of the DkIDL6 gene in the AZ. Moreover, PME and PG activities were significantly lower in Ca-treated fruits, confirming the stabilising effect of calcium on AZ integrity. In summary, pre-anthesis calcium sprays reduced premature fruit drop by about 30% under heat–drought stress by down-regulating key abscission genes (DkIDL6, DkPG20, DkPME41) and preserving cell wall integrity and fruit firmness, supporting the use of Ca treatments as a climate-smart approach to stabilise persimmon yield. Full article

GNAO1 is an alpha subunit of the G-protein complex involved in signal transduction in neurons. The G203R mutation in the GNAO1 gene arises recurrently de novo and causes epileptic encephalopathy and movement disorder. GNAO1 has two main isoforms, GNAO1-A and GNAO1-B, but their functional or expression differences are poorly understood. Molecular functions of GNAO1 are mainly studied in neurons, yet glial cells also express GNAO1 and participate in the pathogenesis of epilepsy. Here, we used human-induced pluripotent stem cell-based models to investigate the localization and expression of GNAO1 isoforms in astrocytes. We showed that in astrocytes, almost 100% of GNAO1 transcripts encoded GNAO1-B with very low GNAO1-A expression. We showed that there were no differences in localization between GNAO1-A and GNAO1-B, both in WT and G203R states. We also showed that GNAO1 localized in astrocytic retraction fibers and migrasomes, structures not previously described in this cell type. We showed that GNAO1-positive retraction fibers of neighboring cells provided cell-to-cell contacts and also provided calcium waves during astrocytic excitation. Overexpression of both GNAO1-A and GNAO1-B tends to lower calcium activity in astrocytes, with GNAO1-A providing the most severe impairment of activity. Our results demonstrate that astrocytes, in addition to neurons, should be used as a model for studying GNAO1-related disorders and that GNAO1 mutations should be evaluated in the context of both the GNAO1-A and GNAO1-B isoforms. Full article

Hypertension, a leading factor for cardiovascular diseases (CVD), is a particularly heavy burden in women during middle age, when cardioprotective hormones begin to decline. The abnormal handling of calcium (Ca²⁺) in vascular smooth muscle cells (VSMCs) leads to increased vasoconstriction, remodeling, and altered arterial compliance during hypertension. The Spontaneously Hypertensive Rats (SHR) is a model of essential hypertension, and middle-aged females with hypertension represent a stage of disease where vascular dysfunction is prominent but understudied. Losartan, a widely prescribed angiotensin II (AngII) receptor (AT1R) blocker, exerts antihypertensive effects by affecting Ang II/Ca²⁺ signaling. However, whether it corrects the Ca²⁺ mishandling in the aorta of middle-aged female SHR has not been established. In this study, the thoracic aorta from 36-week-old female SHRs treated with losartan was assessed for Ca²⁺ mishandling using myography and biochemical assays. Meanwhile, biomechanical properties and stiffness were evaluated using Pulse Wave Velocity (PWV), Atomic Force Microscopy (AFM), and assessments of collagen and elastin contents. Compared with normotensive controls, SHR demonstrated disrupted Ca²⁺ handling, increased stiffness, and Extracellular Matrix (ECM) remodeling in middle-aged females. Treatment with losartan abrogated Ca²⁺ mishandling influx and efflux in the VSMC, decreased stiffness, and restored the aortic structural changes. These findings demonstrate that losartan abolishes Ca²⁺ mishandling and highlight a mechanistic role of AT1R blockade in restoring vascular function in the aorta of middle-aged females during hypertension. Full article

Injectable biomaterials for vocal fold disorders are being developed to provide not only mechanical reinforcement but also a regenerative microenvironment. Recent hydrogels based on hyaluronic acid (HA) derivatives, calcium hydroxylapatite and decellularized matrix scaffolds are designed to approximate the viscoelastic behavior of native tissue, allow controlled degradation, and modulate local immune responses. Rather than serving merely as space-filling agents, several of these materials deliver extracellular matrix (ECM)-like biochemical signals that help maintain pliability and overcome some limitations of conventional augmentation. Experimental and early clinical studies involving growth factor delivery, stem cell-based injections, and ECM-mimetic hydrogels have demonstrated improved mucosal wave vibration and reduced fibrosis in cases of scarring. In clinical series, benefits from basic fibroblast growth factor can persist for up to 12 months. Further progress will depend on correlating material properties with objective vibratory performance to achieve lasting restoration of phonation and advance true tissue-regenerative therapy. Full article

Calcium (Ca²⁺) release from the sarcoplasmic reticulum is central to excitation–contraction coupling and plays a critical role in the development of skeletal muscle fatigue. Altered Ca²⁺ dynamics may affect not only contractile function but also neuromuscular excitability. This study examined the effects of pharmacological modulation of Ca²⁺ channels on fatigue development and spinal reflex activity in rats. Using the Hoffmann reflex (H-reflex) as an indicator of motoneuron excitability, we evaluated the effects of Ca²⁺ channel blockers (Amiloride, Nifedipine) and an activator ((−)-Bay K8644) on the reflex responses of the plantar muscle before and after fatigue induction. The ratio of the maximum H-reflex to maximum M-wave (H_max/M_max) was used to assess alterations in spinal excitability. Compared with the control, both Amiloride and Nifedipine markedly reduce the H_max/M_max ratio (77% and 60%, respectively), whereas (−)-Bay K8644 elicited a robust 129% increase. These findings demonstrate that pharmacological modulation of Ca²⁺ channels has distinct and divergent effects on spinal excitability during fatigue. These results highlight the close interaction between intramuscular Ca²⁺ regulation and reflex pathways and suggest potential strategies for enhancing muscle performance through targeted Ca²⁺ channel modulation. Full article

Vascular calcification (VC) is a multifactorial pathological deposition of calcium in the vasculature and is associated with severe cardiovascular outcomes, particularly in patients with chronic kidney disease (CKD). Various vitamin K analogs have been found to influence the development of VC. We utilized a high-phosphate-induced VC model in mouse vascular smooth muscle cells (VSMCs) and developed an in vivo VC model using ApoE^−/− mice subjected to 5/6 nephrectomy and fed an oral high-phosphorus diet to evaluate the effect of the vitamin K3 analog phthiocol. Transdermal glomerular filtration rate measurement, pulse wave velocity for aortic stiffness assessment, blood biochemical analysis, and pathological examinations were conducted. Phthiocol suppressed reactive oxygen species production and reduced subsequent cell death and calcification in a dose-dependent manner. It inhibited osteogenic trans-differentiation by restoring the PI3K/Akt pathway, activating Nrf2/HO-1 antioxidation signaling, and downregulating IL-1β and TNF-α. The high-phosphate diet in ApoE^−/− CKD mice significantly induced dyslipidemia, renal impairment, hyperphosphatemia, aortic stiffness, and calcium deposition in aortic tissue compared to the control group. Phthiocol treatment markedly improved dyslipidemia, hyperphosphatemia, and aortic stiffness. The vitamin K3 analog phthiocol ameliorates phosphate-induced osteogenic trans-differentiation of VSMCs and subsequent VC by restoring the PI3K/Akt pathway and enhancing Nrf2/HO-1 antioxidant activity. Full article

Osteocytes translate fluid shear stress into biochemical signals critical for bone homeostasis. Here, we combined 3-dimensional (3D) osteocyte culture, microgravity simulation, fluid shear mimicking reloading after disuse, and real-time calcium signaling analysis to elucidate responses of osteocytes under different mechanical environments. Ocy454 cells were seeded onto 3D scaffolds and cultured under static (control) or simulated microgravity (disuse) conditions using a rotating wall vessel bioreactor. Elevated expression levels of Sost, Tnfsf11 (Rankl), and Dkk1 were detected following disuse, confirming efficacy of the microgravity model. Cell membrane integrity under mechanical challenge was evaluated by subjecting scaffold cultures to fluid shear in medium containing FITC-conjugated dextran (10 kDa). The proportion of dextran-retaining cells, indicative of transient membrane disruption and subsequent repair, was higher in microgravity-exposed osteocytes than controls, suggesting increased susceptibility to membrane damage upon reloading following disuse. Intracellular calcium signaling was assessed under a high but physiological fluid shear stress (30 dynes/cm²). Scaffolds cultured under disuse conditions demonstrated a larger sub-population of osteocytes with high calcium signaling intensity (F/Fo > 10 fold) during fluid shear. The maximum fold change in calcium signaling intensity over baseline and the duration of the peak calcium wave were greater for osteocytes cultured under disuse as compared to static controls, however the bioreactor-cultured osteocytes showed, on average, fewer calcium waves than those cultured under control conditions. Subsequent experiments demonstrated that the sub-population of osteocytes with high calcium signaling intensity following exposure to disuse were those that had experienced a transient membrane disruption event during reloading. Together, these results suggest that simulated microgravity enhances osteocyte susceptibility to formation of transient membrane damage and alters intracellular calcium signaling responses upon reloading. This integrated approach establishes a novel platform for mechanistic studies of osteocyte biology and could inform therapeutic strategies targeting skeletal disorders related to altered mechanical loading. Full article

We conducted ultrasonic (1-MHz) laboratory measurements on 210 samples from the Vaca Muerta Formation (Neuquén Basin, Argentina) to determine the factors influencing acoustic velocities in siliciclastic–carbonate mudstone. We quantitatively assessed the calcium carbonate and total organic carbon (TOC) content and qualitatively identified the quartz and clay mineralogy. For brine-saturated samples, P-wave velocities ranged from 2826 to 6816 m/s, S-wave velocities ranged from 1474 to 3643 m/s, and porosity values ranged from 0.01 to 19.4%. Carbonate content percentages, found to be critically important, vary widely from 0.08 to 98.0%, while TOC ranged from 0 to 5.3%. Velocity was primarily controlled by carbonate content and, to a lesser extent, by the non-carbonate mineralogy of the rock (e.g., quartz, clay minerals). TOC content had little effect on the acoustic properties. Due to the low porosity of most samples, mineral composition had a stronger influence on velocity than porosity or pore geometry. The V_p/V_s ratio of dry samples ranged from 1.38 to 1.97 and decreased as porosity increased. In saturated samples, the V_p/V_s ratio ranged from 1.46 to 2.06 and appeared independent of porosity. A clear distinction between carbonate and mixed lithofacies under both saturated and dry conditions was observed in all samples. Full article

Spiral wave dynamics in cardiac tissue are critically implicated in the pathogenesis of arrhythmias. This study investigates the effects of modulating calcium and potassium currents on spiral wave stability in a two-dimensional cardiac model. The gate variable that dynamically regulates the opening probability of ion channels also plays a significant role in the control of the spiral wave dynamics. We demonstrate that reducing gate variables accelerates wave propagation, thins spiral arms, and shortens action potential duration, ultimately inducing dynamic instability. Irregular electrocardiogram (ECG) patterns and altered action potential morphology further suggest an enhanced arrhythmogenic potential. These findings elucidate the ionic mechanisms underlying spiral wave breakup, providing both theoretical insights and practical implications for the development of targeted arrhythmia treatments. Full article

The neurological basis of consciousness remains unknown despite innumerable theories proposed for over a century. The major obstacle is that empirical studies demonstrate that all sensory information is subdivided and parcellated as it is processed within the brain. A central region where such diverse information combines to form conscious expression has not been identified. A novel hypothesis was introduced over two decades ago that proposed astrocytes, with their ability to interconnect to form a global syncytium within the neocortex, are the locus of consciousness based on their ability to integrate synaptic signals. However, it was criticized because intercellular calcium waves, which are initiated by synaptic activity, are too slow to contribute to consciousness but ideal for memory formation. Although astrocytes are known to exhibit rapid electrical responses in active sensory pathways (e.g., vision), it was technically impossible to determine electrical activity within the astroglia syncytium because of the challenge of separating syncytial electrical responses from simultaneous neuronal electrical activity. Therefore, research on astroglia syncytial electrical activity lagged for over sixty years, until recently, when an ingenuous technique was developed to eliminate neuronal electrical interference. These technical advances have demonstrated that the astroglia syncytium, although massive and occupying the entire neocortex, is isoelectric with minimal impedance. Most importantly, the speed of electrical conductance within the syncytium is as rapid as that of neural networks. Therefore, the astroglia syncytium is theoretically capable of transmitting integrated local synaptic signaling globally throughout the entire neocortex to bind all functional areas of the brain in a timeframe required for consciousness. Full article

Erosion poses significant threats to infrastructures and ecosystems, exacerbated by climate change-driven sea-level rise and intensified wave actions. Microbially induced calcium carbonate precipitation (MICP) has emerged as a promising, sustainable, and eco-friendly solution for erosion mitigation. This review synthesizes recent advancements in optimizing biomineralization efficiency, multi-scale erosion control, and field-scale MICP implementations in marine dynamic conditions. Key findings include the following: (1) Kinetic analysis of Ca²⁺ conversion confirmed complete ion utilization within 24 h under optimized PA concentration (3%), resulting in a compressive strength of 2.76 MPa after five treatment cycles in ISO-standard sand. (2) Field validations in Ahoskie and Sanya demonstrated the efficacy of MICP in coastal erosion control through tailored delivery systems and environmental adaptations. Sanya’s studies highlighted seawater-compatible MICP solutions, achieving maximum 1743 kPa penetration resistance in the atmospheric zone and layered “M-shaped” CaCO₃ precipitation in tidal regions. (3) Experimental studies revealed that MICP treatments (2–4 cycles) reduced maximum scour depth by 84–100% under unidirectional currents (0.3 m/s) with the maximum surface CaCO₃ content reaching 3.8%. (4) Numerical simulations revealed MICP enhanced seabed stability by increasing vertical effective stress and reducing pore pressure. Comparative analysis demonstrates that while the destabilization depth of untreated seabed exhibits a linear correlation with wave height increments, MICP-treated seabed formations maintain exceptional stability through cohesion-enhancing properties, even when subjected to progressively intensified wave forces. This review supports the use of biomineralization as a sustainable alternative for shoreline protection, seabed stabilization, and offshore foundation integrity. Full article

Long-range intercellular communication is essential for multicellular biological systems to regulate multiscale cell–cell interactions and maintain life. Growing evidence suggests that intercellular calcium waves (ICWs) act as a class of long-range signals that influence a broad spectrum of cellular functions and behaviors. Importantly, mechanical signals, ranging from single-molecule-scale to tissue-scale in vivo, can initiate and modulate ICWs in addition to relatively well-appreciated biochemical and bioelectrical signals. Despite these recent conceptual and experimental advances, the full nature of underpinning mechanotransduction mechanisms by which cells convert mechanical signals into ICW dynamics remains poorly understood. This review provides a systematic analysis of quantitative ICW dynamics around three main stages: initiation, propagation, and regeneration/relay. We highlight the landscape of upstream molecules and organelles that sense and respond to mechanical stimuli, including mechanosensitive membrane proteins and cytoskeletal machinery. We clarify the roles of downstream molecular networks that mediate signal release, spread, and amplification, including adenosine triphosphate (ATP) release, purinergic receptor activation, and gap junction (GJ) communication. Furthermore, we discuss the broad pathophysiological implications of ICWs, covering pathophysiological processes such as cancer metastasis, tissue repair, and developmental patterning. Finally, we summarize recent advances in optical imaging and artificial intelligence (AI)/machine learning (ML) technologies that reveal the precise spatial-temporal-functional dynamics of ICWs and ATP waves. By synthesizing these insights, we offer a comprehensive framework of ICW mechanobiology and propose new directions for mechano-therapeutic strategies in disease diagnosis, cancer immunotherapies, and drug discovery. Full article

Background/Objectives: Calcific tendinopathy of the shoulder is a degenerative condition characterized by calcium deposits within the rotator cuff tendons, particularly the supraspinatus. It is a frequent cause of chronic shoulder pain and functional limitation, adversely affecting quality of life. While conservative treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, and corticosteroid injections are commonly used, extracorporeal shock wave therapy (ESWT) has emerged as a promising non-invasive alternative. This interventional clinical trial compared the efficacy of ultrasound-guided versus landmark-based ESWT in treating calcific tendinopathy. Methods: Eighty-four patients with ultrasound-confirmed calcific tendinopathy were randomized into two groups. Group 1 received ultrasound-guided ESWT with real-time targeting of the deposit; Group 2 received landmark-based ESWT based on anatomical palpation. Both groups underwent three sessions (2000 impulses at 2.2 bars, energy level 5, 8 Hz). Clinical outcomes were assessed using the Constant–Murley score (CMS) at baseline, 12 weeks, and 6 months. Calcific deposit resorption was evaluated via ultrasound imaging. Results: The ultrasound-guided group showed a significant improvement in CMS from a median of 50 (range: 30–75) at baseline to 97 (52–100) at 6 months. The landmark-based group also improved, from 48 (32–74) to 79 (40–96). At 6 months post-treatment, 90.9% of patients in the ultrasound-guided group achieved successful outcomes (CMS ≥ 86), compared to 50% in the landmark-based group. Complete calcific resorption occurred in 65.9% of patients in Group 1, compared to 50% in Group 2; 15% of patients in Group 2 showed no resorption. Conclusions: Ultrasound-guided ESWT was significantly more effective than landmark-based ESWT in improving shoulder function, reducing pain, and promoting calcific deposit resorption. These findings support ultrasound guidance as a preferred approach for optimizing ESWT outcomes in patients with calcific tendinopathy of the shoulder. Full article

Background and Objectives: Cardiovascular diseases are prevalent entities, especially in emergency patients. Arterial stiffness is a known predictor of cardiovascular risk and mortality and is quantified by carotid-femoral pulse wave velocity (cfPWV). It is caused in part by vascular calcification, but exact details of the underlying mechanisms are yet to be elucidated, and current data suggest endocrine influences. This study thus aimed to assess the associations of endocrine parameters, particularly thyroid and parathyroid hormones, calcium, inorganic phosphate, and vitamin D, with cfPWV as a surrogate for arterial stiffness. Materials and Methods: Adults presenting to a single tertiary care emergency department in Vienna between 2018 and 2023 were prospectively enrolled. CfPWV was measured non-invasively, and levels of thyroid and parathyroid hormones and 25-hydroxyvitamin D, calcium, and inorganic phosphate were assessed. Results: In total, data from 827 patients, predominantly male (57%) and around 60 (47–72) years of age, were assessed. We observed a significant worsening of cfPWV with increasing parathyroid hormone levels (p < 0.001) and TSH levels (p = 0.03). No significant influences of calcium, inorganic phosphate, or 25-hydroxyvitamin D were observed. Conclusions: Thyroid and parathyroid hormone levels are associated with arterial stiffness in emergency department patients, suggesting a need for a comprehensive workup in patients at risk because of comorbidities and age. Additional prospective studies are needed to further elucidate the role of endocrinology in arterial stiffness and the subsequent relevance in emergency medicine. Full article