Cyclic Changes Research Articles

How do extreme fluctuations in water level affect fish condition in Amazonian Floodplain Lakes?

The annual flood pulse is a defining feature of Amazonian floodplain lakes, creating a highly variable environment that influences resource availability, such as food and habitat. These cyclical changes necessitate a high degree of adaptability among fish species, many of which have evolved specialized strategies to cope with the fluctuating conditions. In 2023, the Amazon basin experienced a record-breaking drought event, leading to mass mortality of Amazonian fish and other wildlife. This study examines the effect of this extreme event on fish condition in white-water (Rio Solimões basin) and black-water (Rio Negro basin) floodplain lakes. These contrasting environments provide a unique opportunity to study how different water qualities and extreme water-level fluctuations impact fish condition. Research was conducted during the normal low-water period in November 2019 and the drastically decreased water levels in November 2023. The main objective was to understand how extreme water-level fluctuations affect fish health and nutritional status. A total of 585 fishes were analyzed, with 294 from white-water and 291 from black-water, representing different feeding types to provide a comprehensive picture of changes in fish condition. Water-level changes had a statistically significant impact on fish condition in both areas. Comparing low-water and extreme low-water levels, fish condition was consistently higher during the normal low-water period. The linear mixed-effects model revealed that the intensity of the low-water season had a significant effect on fish length-adjusted mass, suggesting that the decrease in water level is associated with an overall decrease in fish length-adjusted mass. When comparing the mean water-level effect (Glass's Δ) between low-water and extreme low-water levels, we found a bigger effect in the black-water system than in the white-water system. This difference may be attributed to the lower nutrient content and higher levels of humic acids and refractory dissolved organic matter in black-water, which can further limit primary productivity and food availability for fishes.

Cyclical accretion regime change in the slow X-ray pulsar 4U 0114+65 observed with Chandra

4U 0114+65 is a high-mass X-ray binary system formed by the luminous supergiant B1Ia, known as V V662 Cas, and one of the slowest rotating neutron stars (NSs) with a spin period of about 2.6 hours. This provides a rare opportunity to study interesting details of the accretion within each individual pulse of the compact object. For this paper we analyzed 200 ks of Chandra grating data, divided into nine uninterrupted observations around the orbit. The changes in the circumstellar absorption column through the orbit suggest an orbital inclination of ∼ 40^∘ with respect to the observer and a companion mass-loss rate of ∼ 8.6 10^-7 M yr^-1. The peaks of the NS pulse exhibit a large pulse-to-pulse variability. Three of them show an evolution from a brighter regime to a weaker one. We propose that the efficiency of Compton cooling in this source fluctuates throughout an accumulation cycle. After significant depletion of matter within the magnetosphere, since the settling velocity is ∼ 2 lower than the free-fall velocity, the source gradually accumulates matter until the density exceeds a critical threshold. This increase in density triggers a transition to a more efficient Compton cooling regime, leading to a higher mass accretion rate and consequently to an increased brightness.

Operation of spinal sensorimotor circuits controlling phase durations during tied-belt and split-belt locomotion after a lateral thoracic hemisection.

Locomotion is controlled by spinal circuits that interact with supraspinal drives and sensory feedback from the limbs. These sensorimotor interactions are disrupted following spinal cord injury. The thoracic lateral hemisection represents an experimental model of an incomplete spinal cord injury, where connections between the brain and spinal cord are abolished on one side of the cord. To investigate the effects of such an injury on the operation of the spinal locomotor network, we used our computational model of cat locomotion recently published in eLife (Rybak et al., 2024) to investigate and predict changes in cycle and phase durations following a thoracic lateral hemisection during treadmill locomotion in tied-belt (equal left-right speeds) and split-belt (unequal left-right speeds) conditions. In our simulations, the 'hemisection' was always applied to the right side. Based on our model, we hypothesized that following hemisection the contralesional ('intact', left) side of the spinal network is mostly controlled by supraspinal drives, whereas the ipsilesional ('hemisected', right) side is mostly controlled by somatosensory feedback. We then compared the simulated results with those obtained during experiments in adult cats before and after a mid-thoracic lateral hemisection on the right side in the same locomotor conditions. Our experimental results confirmed many effects of hemisection on cat locomotion predicted by our simulations. We show that having the ipsilesional hindlimb step on the slow belt, but not the fast belt, during split-belt locomotion substantially reduces the effects of lateral hemisection. The model provides explanations for changes in temporal characteristics of hindlimb locomotion following hemisection based on altered interactions between spinal circuits, supraspinal drives, and somatosensory feedback.

Carbonate fluorapatite coatings on phillipsite represent a significant sink of phosphorus in abyssal plains of the western Pacific Ocean

As an essential micronutrient, phosphorus plays a key role in oceanic biogeochemistry, with its cycling intimately connected to the global carbon cycle and climate change. Authigenic carbonate fluorapatite (CFA) has been suggested to represent a significant phosphorus sink in the deep ocean, but its formation mechanisms in oceanic low-productivity settings remain poorly constrained. Applying X-ray absorption near edge structure, transmission electron microscopy, and laser ablation inductively coupled plasma mass spectrometer analyses, we report a unique mineral assemblage where CFA crystals coat phillipsite in abyssal sediments of the East Mariana Basin and the Philippine Sea. This finding suggests that phillipsite provides an ideal microenvironment for CFA formation due to its ability to release calcium cations and its strong adsorption capacity for phosphate anions. The feasibility of such a mechanism was confirmed by long-term (10 mo) laboratory experiments. Furthermore, the CFA forming in the sediment of abyssal plains is found to be enriched in rare earth elements (REE). The previously unrecognized mechanism of CFA formation may therefore not only contribute to the cycling of phosphorus in oceanic low-productivity environments but may also represent a significant sink of REE.

Spatial and Temporal Variations in Soil Organic Carbon in Northwestern China via Comparisons of Different Methods

Soil organic carbon (SOC) is a crucial component for investigating carbon cycling and global climate change. Accurate data exhibiting the temporal and spatial distributions of SOC are very important for determining the soil carbon sequestration potential and formulating climate strategies. An important scheme of mapping SOC is to establish a link between environmental factors and SOC via different methods. The Shiyang River Basin is the third largest inland river basin in the Hexi Corridor, which has closed geographical conditions and a relatively independent carbon cycle system, making it an ideal area for carbon cycle research in arid areas. In this study, 65 SOC samples were collected and 21 environmental factors were assessed from 2011 to 2021 in the Shiyang River Basin. The linear regression (LR) method and two machine learning methods, i.e., support vector machine regression (SVR) and random forest (RF), are applied to estimate the spatial distribution of SOC. RF is slightly better than SVR because of its advantages in the comparison of classification. When latitude, slope, and the normalized vegetation index (NDVI) are used as predictor variables, the best SOC performance is shown. Compared with the Harmonized World Soil Database (HWSD), the optimal scheme improved the accuracy of the SOC significantly. Finally, the spatial distribution of SOC tended to increase, with a total increase of 135.94 g/kg across the whole basin. The northwestern part of the middle basin decreased by 2.82% because of industrial activities. The SOC in Minqin County increased by approximately 62.77% from 2011 to 2021. Thus, the variability of the spatial SOC increased. This study provides a theoretical basis for the spatial and temporal distributions of SOC in inland river basins. In addition, this study can also provide effective and scientific suggestions for carbon projects, offer a key scientific basis for understanding the carbon cycle, and support global climate change adaptation and mitigation strategies.

A Comparative Spatiotemporal Analysis for Long-Term Trends of Hydrometeorological Variables in Maritsa River Basin

Revealing long-term trends in hydrometeorological variables plays a critical role in the sustainable management and planning of water resources. These analyses are necessary to understand climate change impacts, taking precautions for natural disasters, plan agricultural activities, and develop water management strategies. The aim of this study is to examine the changes in monthly and annual total precipitation and evapotranspiration values in the Maritsa River Basin, a transboundary water basin between Bulgaria, Greece, and Türkiye. For this, precipitation values for the 1982-2023 water years were taken from the Climate Hazards Group InfraRed Precipitation with Stations (CHIRPS) data set, and evapotranspiration values for the 1982-2023 water years were taken from the European Reanalysis 5th Generation-Land (ERA5-Land) data set. The Mann-Kendall, Sen's slope estimator, and Innovative Trend Analysis (ITA) methods were used to determine trends. According to the test results, there is a statistically significant increase in annual total precipitation values within the 95% confidence interval and in annual total evapotranspiration values within the 99% confidence interval. Specifically with all three methods positive and statistically significant trends are observed in precipitation in October, January, May and June. In the monthly evapotranspiration trend analysis, a statistically significant increase is observed except for November, December, June and July. Trend increases were visualized using the graphical method ITA. Significant increasing trends in both monthly and annual precipitation and evapotranspiration reveal changes in the hydrological cycle of the basin. The test results can be used in planning and solving problems related to the basin area.

TFII-I/GTF2I regulates globin gene expression and stress response in erythroid cells.

Transcription factor TFII-I/GTF2I is ubiquitously expressed and has been shown to play a role in the differentiation of hematopoietic cells and in the response to various cellular stressors. We previously demonstrated that TFII-I acts as a repressor of adult β-globin gene transcription and positively regulates expression of stress response proteins, including ATF3. Here we analyzed the function of TFII-I in TF-1 cells during erythroid differentiation and in response to cellular stress, including unfolded protein response, hypoxia, and oxidative stress. Ablation of TFII-I leads to mild changes in cell cycle and proliferation of TF-1 cells. Importantly, TFII-I deficiency increased expression of the adult β-globin gene with concomitant reduction in the expression of the fetal γ-globin genes during erythropoietin mediated erythroid differentiation of TF-1 cells. Furthermore, TFII-I regulates genes involved in stress response, including CHOP, Elongin A, ATF3, ATF4, and Grp78, and participates in the apoptotic response to stressors. In summary, the data provide further support for a role of TFII-I in stress response and in the regulation of globin genes.

Study on the effects of Mogroside V in inhibiting NLRP3-mediated granulosa cell pyroptosis and insulin resistance to improve PCOS

ObjectivePolycystic Ovary Syndrome (PCOS) is a prevalent endocrinopathy in reproductive-aged women, contributing to 75% of infertility cases due to ovulatory dysfunction. The condition poses significant health and psychological challenges, making the study of its pathogenesis and treatment a research priority. This study investigates the effects of Mogroside V (MV) on PCOS, focusing on its anti-inflammatory and anti-insulin resistance properties.MethodsForty-five female Sprague–Dawley rats were divided into three groups: control, PCOS model, and MV treatment. The PCOS model was induced using a high-fat diet and letrozole. The MV treatment group was subsequently administered MV after the establishment of the PCOS model. The study monitored body mass, assessed estrous cycle changes, and measured serum hormone levels. Transcriptome sequencing and bioinformatics were used to identify differentially expressed genes related to inflammation and insulin resistance. Expression of pyroptosis and insulin resistance markers was analyzed using qRT-PCR, Western blot, and IHC. Additionally, an in vitro model assessed MV's impact on inflammation and insulin resistance.ResultsThe PCOS group exhibited elevated serum testosterone (T), luteinizing hormone (LH), insulin, and fasting glucose levels, along with increased insulin resistance (HOMA-IR) and decreased estradiol (E2), which were reversed by MV treatment. Transcriptome analysis identified significant gene expression changes between groups, particularly in pathways related to NLRP3 inflammation and insulin metabolism. MV treatment normalized the expression of ovarian pyroptosis factors (NLRP3, Caspase-1, GSDMD) and inflammatory cytokines (IL-1β, IL-18). In cellular models, MV increased E2 levels, reduced LDH release, and decreased the expression of insulin resistance and pyroptosis markers. Correlation analysis showed pyroptosis factors were positively correlated with HOMA-IR and IGF1, and negatively with IGF1R and E2 levels.ConclusionMV improves PCOS by reducing pyroptosis and insulin resistance, enhancing insulin sensitivity, and promoting estrogen synthesis, thereby restoring granulosa cell function and follicular development.

Animal experiments and network pharmacology to explore the anti-inflammatory mechanism of dapagliflozin in the treatment of polycystic ovary syndrome

Background Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder associated with chronic low-grade inflammation of the ovary. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of antidiabetic drugs that can reduce the weight and hyperglycemia of type 2 diabetes patients. Dapagliflozin is a highly selective, orally active and reversible inhibitor of the human SGLT2. However, the role of dapagliflozin in regulating PCOS remains unclear. Methods In this study, 24 six-week-old female Sprague Dawley (SD) rats were randomly divided into control, letrozole, and letrozole + dapagliflozin groups. PCOS model rats were produced by gavage administration of letrozole for 21 days. The intervention was conducted after the gavage administration of dapagliflozin for 14 days to evaluate the estrous cycle and ovarian imaging changes of the rats in each group. We observed changes in the weight, ovarian weight, and ovarian morphology of the rats in each group. Pathological changes in the ovaries were examined by H&E staining, changes in ovarian tissue cell apoptosis were identified using TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and changes in inflammation-related factors were detected using immunohistochemistry and Western blotting analysis. Network pharmacology was used to predict the inflammatory targets and pathways affected by dapagliflozin in treating PCOS, and the potential interactions between dapagliflozin and inflammation-related target proteins were evaluated through molecular docking. Results Our results demonstrated that dapagliflozin treatment significantly improved PCOS symptoms, recovered ovarian morphology and physiological functions, and reduced the apoptosis of ovarian cells after drug intervention. Dapagliflozin treatment also reduced the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, indicating its anti-inflammatory properties. Furthermore, network pharmacology identified 26 intersecting target genes relevant to inflammation in PCOS, with subsequent molecular docking simulations revealing strong binding affinities of dapagliflozin to key targets, including AKT1 and TP53. Conclusions These findings suggest that dapagliflozin exerts beneficial effects on PCOS by ameliorating ovarian dysfunction and reducing inflammation. Dapagliflozin represents a promising therapeutic candidate for managing PCOS, warranting further clinical investigation to explore its full potential in treating this multifaceted disorder.

Effects of fine terrain complexity on cloud and precipitation changes over the Tibetan Plateau: a modeling study

Inaccurate characterization of complex topography leads to the wet bias in climate models, particularly affecting terrain effects in regions like the Tibetan Plateau (TP). This study utilizes the Weather Research and Forecasting (WRF) model with multiple terrain datasets and introduces the terrain complexity index (TCI) to quantify the degree of terrain changes, aiming to evaluate how terrain complexity affects the cloud and precipitation processes over the TP. The results indicate that fine terrain complexity primarily causes earlier cloud formation and precipitation, resulting in more heavy precipitation on the southern slope of the TP (SSTP) and more light precipitation on the TP platform. The structure of moisture transport and microphysical processes further reveals that this promotes the formation of more medium and high clouds, increasing the proportion of solid precipitation over the SSTP. Over the TP platform, the restriction of medium and high cloud development with enhancing the proportion of low clouds for more liquid precipitation. These findings deepen the understanding of the TP’s complex terrain effect on cloud and precipitation changes in the Asian water cycle.

Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA

The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers. Proteomic alterations were analyzed using label-free shotgun and targeted LC–MS/MS. MS275 enhanced the sensitivity of A549 cells to pemetrexed, but only when administered following prior treatment with pemetrexed. Both HeLa (p53 negative) and A549 (p53 positive) showed robust activation of γH2AX upon treatment with this combination. Importantly, CRISPR/Cas9 knockout of the uracil-DNA glycosylase UNG did not affect γH2AX activation or sensitivity to pemetrexed. Proteomic analysis revealed that MS275 altered the expression of known pemetrexed targets, as well as several proteins involved in pyrimidine metabolism and DNA repair, which could potentiate pemetrexed cytotoxicity. Contrary to the conventional model of antifolate toxicity, which implicates futile cycles of uracil incorporation and excision in DNA, we propose that ribonucleotide incorporation in nuclear and mitochondrial DNA significantly contributes to the cytotoxicity of antifolates like pemetrexed, and likely also of fluorinated pyrimidine analogs. HDAC inhibition apparently exacerbates cytotoxicity of these agents by inhibiting error-free repair of misincorporated ribonucleotides in DNA. The potential of HDACis to modulate pyrimidine metabolism and DNA damage responses offers novel strategies for improving NSCLC outcomes.

Profound Changes in the Seasonal Cycle of Sea Level Along the United States Mid‐Atlantic Coast

AbstractThe monthly mean sea level along the U.S. Mid‐Atlantic Coast varies seasonally, reaching a minimum in January and a maximum in September during the 1960–2020 period. However, this seasonal cycle has changed significantly on multi‐decadal timescales. In the last two decades, the annual minimum has shifted from January to February. The amplitude of seasonal changes increased by 65% from 14.16 cm in 1980–1999 to 23.16 cm in 2000–2020. Even more concerning, the maximum sea level in September rose by 82%, from 6.81 to 12.38 cm, potentially exacerbating coastal flooding over the past 20 years. A two‐layer ocean model effectively replicates both the phase and magnitude of the observed changes and attributes these shifts to changes in wind stress near the coast, with relatively minor influence from deep ocean forcing. Both alongshore and cross‐shore wind stress changes are found to contribute to changes in the sea level's seasonal cycle.

Study of cyclic price volatility for fish products in Russia

The purpose of the work: to test the hypothesis about the existence of periodically changing price volatility over time and to determine the key characteristics of this process.Methods used: decomposition of price dynamics for the main types of fish products in Russia with the allocation and analysis of its components; to construct a model describing the trajectory of price changes, the provisions of the spider web theory were used, in particular, the Kagan model, transformed into the harmonic oscillator model.Results: it was found that prices for fish products in the Russian Federation, in addition to the general upward trend, also have cyclical volatility and are subject to shock changes from time to time; the parameters of price fluctuations were determined.Scientific novelty: A nonlinear model has been developed that reflects in aggregate form the influence of endogenous and exogenous factors on prices for fish products. The model describes cyclical price changes in the form of relaxation fluctuations.Practical significance: The study of the recessive characteristics of price volatility made it possible to identify the key parameters of possible measures of industry policy. These measures can become part of the socioeconomic policy.

Spatiotemporal distribution of global peatland area during the Holocene

Peatlands are a key component of terrestrial ecosystems, and their development has an important impact on global carbon cycle and climate change. However, the long-term evolution of global peatlands remains uncertain, particularly their spatial distribution. We compiled 4700 basal peatland data during Holocene, and 669 pollen data of Sphagnum with basal and end ages, to allow a more robust reconstruction of the spatial distribution of peatlands. Using buffer analysis (BA) and inverse distance weighted (IDW) interpolation of peat data, we reconstructed spatiotemporal changes in global peatland area at a spatial resolution of 0.5° × 0.5° for every 1,000 years period during Holocene. The results show that peatland area have expanded substantially in North America, Europe, and Western Siberia during early-Holocene, and increased rapidly from 2.18(0.32) Mkm2 to 4.03(3.08) Mkm2 during 12-6 ka BP, then slowly to 4.15(4.23) Mkm2 after 6 ka BP according to BA (IDW) methods. The database will be useful for analyzing the global/regional terrestrial carbon cycle and climate change during Holocene, especially for modeling peatland methane emissions.

Change in dominant orbital cycles led to warm excursions during the middle−late Eocene cooling

Change in dominant orbital cycles led to warm excursions during the middle−late Eocene cooling

Longitudinal Changes in Pitch-Related Acoustic Characteristics of the Voice Throughout the Menstrual Cycle: Observational Study.

Identifying subtle changes in the menstrual cycle is crucial for effective fertility tracking and understanding reproductive health. The aim of the study is to explore how fundamental frequency features vary between menstrual phases using daily voice recordings. This study analyzed smartphone-collected voice recordings from 16 naturally cycling female participants, collected every day for 1 full menstrual cycle. Fundamental frequency features (mean, SD, 5th percentile, and 95th percentile) were extracted from each voice recording. Ovulation was estimated using luteinizing hormone urine tests taken every morning. The analysis included comparisons of these features between the follicular and luteal phases and the application of changepoint detection algorithms to assess changes and pinpoint the day in which the shifts in vocal pitch occur. The fundamental frequency SD was 9.0% (SD 2.9%) lower in the luteal phase compared to the follicular phase (95% CI 3.4%-14.7%; P=.002), and the 5th percentile of the fundamental frequency was 8.8% (SD 3.6%) higher (95% CI 1.7%-16.0%; P=.01). No significant differences were found between phases in mean fundamental frequency or the 95th percentile of the fundamental frequency (P=.65 and P=.07). Changepoint detection, applied separately to each feature, identified the point in time when vocal frequency behaviors shifted. For the fundamental frequency SD and 5th percentile, 81% (n=13) of participants exhibited shifts within the fertile window (P=.03). In comparison, only 63% (n=10; P=.24) and 50% (n=8; P=.50) of participants had shifts in the fertile window for the mean and 95th percentile of the fundamental frequency, respectively. These findings indicate that subtle variations in vocal pitch may reflect changes associated with the menstrual cycle, suggesting the potential for developing a noninvasive and convenient method for monitoring reproductive health. Changepoint detection may provide a promising avenue for future work in longitudinal fertility analysis.

Effect of temperature on circadian clock functioning of trees in the context of global warming.

Plant survival in a warmer world requires the timely adjustment of biological processes to cyclical changes in the new environment. Circadian oscillators have been proposed to contribute to thermal adaptation and plasticity. However, the influence of temperature on circadian clock performance and its impact on plant behaviour in natural ecosystems are not well-understood. We combined bioinformatics, molecular biology and ecophysiology to investigate the effects of increasing temperatures on the functioning of the circadian clock in two closely related tree species from Patagonian forests that constitute examples of adaptation to different thermal environments based on their altitudinal profiles. Nothofagus pumilio, the species from colder environments, showed a major rearrangement of its transcriptome and reduced ability to maintain rhythmicity at high temperatures compared with Nothofagus obliqua, which inhabits warmer zones. In altitude-swap experiments, N. pumilio, but not N. obliqua, showed limited oscillator function in warmer zones of the forest, and reduced survival and growth. Our findings show that interspecific differences in the influence of temperature on circadian clock performance are associated with preferred thermal niches, and to thermal plasticity of seedlings in natural environments, highlighting the potential role of a resonating oscillator in ecological adaptation to a warming environment.

Biomechanical effects of saddle height changes in leisure cycling with unilateral transtibial prostheses: A simulated study.

Cycling is a beneficial physical activity for rehabilitating individuals with lower-limb amputations and serves as a feasible leisure sport. However, the optimal bicycle configuration for cycling with a unilateral transtibial prosthesis at leisure levels has not been investigated. For saddle height at professional cycling levels, existing literature suggests utilizing the same configuration as that used by intact cyclists, where the knee reaches 25-35° at maximum extension. However, leisure cyclists tend to select lower saddle heights, and cycling with a unilateral transtibial prosthesis infers altered biomechanics during cycling practice. This study aimed to investigate the effects of cycling at different saddle heights with a simulated unilateral prosthesis. Ten able-bodied participants wore orthoses to simulate prosthetic conditions. The experimental task was performed on an ergometer at 40 W resistance, 60 rpm to simulate leisure cycling. Standard saddle height was defined as maximum knee extension of 45°. This height was used as the control condition and its trials were performed without orthoses. The variable heights were set as height percentage variations (-7%, -3.5%, 0, +3.5%, and +7%). Muscle activity, joint movement, force application to the pedals, perceived exertion, and comfort were evaluated. The -3.5% and -7% saddle heights resulted in joint movement and muscle activity levels closer to those in the control conditions, which also showed improved power symmetry between the affected and non-affected legs. In addition, the -3.5% height increased comfort level in participants. In conclusion, selecting lower saddle heights may be beneficial for unilateral transtibial amputees during leisure cycling. The optimal saddle height for this population may maintain maximum knee extension within the 37-45° range, dynamically measured on the affected side.

Static Magnetic Field Exposure Causes Small Cell Cycle Disruptions and Changes in Reactive Oxygen Species Levels in Ionizing Radiation Exposed Human Neuroblastoma Cells.

Although static magnetic fields (SMFs) have been reported to induce only minimal biological effects, it has been proposed that they may alter the effects of other agents, such as ionizing radiation. We sham-exposed or exposed human SH-SY5Y neuroblastoma cells to 0.5-, 1.5-, 2.5-, or 3.5-mT SMFs for 24 h either before or after irradiation at 0, 0.4 or 2.0 Gy. After the exposures, cell cycle distribution (subG1 for apoptosis), reactive oxygen species (ROS) levels, caspase-3 activity, and clonogenic survival were assayed. Increase of G0/G1 and decrease of S phase cells was observed in samples exposed to a 3.5-mT SMF after irradiation. The same exposure schedule with a 1.5-mT SMF was associated with an increase of S phase cells, and an increase in ROS levels. Conversely, a decrease in ROS levels was observed in cells exposed to a 2.5-mT SMF before ionizing radiation. No cell cycle changes were observed with SMF exposures before irradiation. Caspase-3 activity or clonogenic survival was not affected by SMF exposures, irrespective of the exposure schedule. In conclusion, small changes in cell cycle distribution and ROS levels were observed in SH-SY5Y cells exposed to SMFs, with more prominent effects observed when SMF exposure was applied after irradiation. Our results suggest that SMF-induced effects show no linear dependency on magnetic flux density below 5 mT. Notably, SMF exposures did not significantly potentiate the effects of ionizing radiation but rather caused an independent additive effect. Bioelectromagnetics. 00:00-00, 2024.

Resetting of the Human Circadian Melatonin Rhythm by Ambient Hypoxia.

Circadian clocks in the body drive daily cycles in physiology and behavior. A master clock in the brain maintains synchrony with the environmental day-night cycle and uses internal signals to keep clocks in other tissues aligned. Work in cell cultures uncovered cyclic changes in tissue oxygenation that may serve to reset and synchronize circadian clocks. Here we show in healthy humans, following a randomized controlled single-blind counterbalanced crossover study design, that one-time exposure to moderate ambient hypoxia (FiO2 ~15%, normobaric) for ~6.5 h during the early night advances the dim-light onset of melatonin secretion by 9 min (95% CI: 1-16 min). Exposure to moderate hypoxia may thus be strong enough to entrain circadian clocks to a 24-h cycle in the absence of other entraining cues. Together, the results provide direct evidence for an interaction between the body's hypoxia-sensing pathway and circadian clocks. The finding offers a mechanism through which behaviors that change tissue oxygenation (e.g., exercise and fasting/eating) can affect circadian timing and through which hypoxia-related diseases (e.g., obstructive sleep apnea and chronic obstructive pulmonary disease) can result in circadian misalignment and associated pathologies. Trial Registration: Registration number: DRKS00023387; German Clinical Trials Register: http://www.drks.de.