Organ Level Research Articles

Limiting cap-dependent translation increases 20S proteasomal degradation and protects the proteomic integrity in autophagy-deficient skeletal muscle.

Postmitotic skeletal muscle critically depends on tightly regulated protein degradation to maintain proteomic stability. Impaired macroautophagy/autophagy-lysosomal or ubiquitin-proteasomal protein degradation causes the accumulation of damaged proteins, ultimately accelerating muscle dysfunction with age. While in vitro studies have demonstrated the complementary nature of these systems, their interplay at the organism levels remains poorly understood. Here, our study reveals novel insights into this complex relationship in autophagy-deficient skeletal muscle. We demonstrated that despite a compensatory increase in proteasome level in response to autophagy impairment, 26S proteasome activity was not proportionally enhanced in autophagy-deficient skeletal muscle. This functional deficit was partly attributed to reduced ATP levels to fuel the 26S proteasome. Remarkably, we found that activation of EIF4EBP1, a crucial inhibitor of cap-dependent translation, restored and even augmented proteasomal function through dual mechanisms. First, genetically activating EIF4EBP1 enhanced both ATP-dependent 26S proteasome and ATP-independent 20S proteasome activities, thereby expanding overall protein degradation capacity. Second, EIF4EBP1 activation caused muscle fiber transformation and increased mitochondrial biogenesis, thus replenishing ATP levels for 26S proteasome activation. Notably, the improved performance of the 20S proteasome in EIF4EBP1-activated skeletal muscle was attributed to an increased abundance of the immunoproteasome, a subtype specially adapted to function under oxidative stress conditions. This dual action of EIF4EBP1 activation preserved proteomic integrity in autophagy-deficient skeletal muscle. Our findings uncover a novel role of EIF4EBP1 in improving protein quality control, presenting a promising therapeutic strategy for autophagy-related muscular disorders and potentially other conditions characterized by proteostatic imbalance.

Widespread environmental contamination from relic munitions in the southwestern Baltic Sea.

Relic munitions from warfare and intentional dumping contaminate coastal waters worldwide, with an estimated 300,000 tons in the German Baltic Sea alone. These contain toxic conventional explosive chemicals, including 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazinane (RDX), and 1,3-dinitrobenzene (DNB). Corrosion of metal munition housings in seawater releases these munition chemicals (MCs) to the marine environment. The current study performed detailed environmental sampling throughout German waters of the southwest Baltic Sea in 2017 and 2018, and measured MCs in water, suspended particles, and sediments. At least one MC was detected in nearly every water sample, from sub-pmol/L up to several thousand pmol/L. Most MC were in the dissolved phase, not on suspended particles, and MC content in sediments was patchy and generally low. TNT levels were especially high in Kiel Bay, whereas RDX and DNB concentrations were highest in Lübeck Bay, likely reflecting regional differences in munitions types. A TNT module was developed and implemented in the General Estuarine Transport Model (GETM), incorporating TNT input to the water column by dissolution and removal by microbial degradation/transformation. Simulated TNT distributions matched observed environmental patterns well, indicating good parametrization of the primary controls. Dissolved concentrations of the target MCs were generally far below acute or chronic toxicity levels for aquatic organisms, but the highest observed concentrations approached toxic levels, especially for DNB. The inventory of dissolved MC in the study region was approximately 3000kg, implying that current contamination levels can be sustained continuously for over 800 years by existing munitions on the seafloor.

Influence of diabetes mellitus on metabolic networks in lung cancer patients: an analysis using dynamic total-body PET/CT imaging.

The intricate interplay between organs can give rise to a multitude of physiological conditions. Disruptions such as inflammation or tissue damage can precipitate the development of chronic diseases such as tumors or diabetes mellitus (DM). While both lung cancer and DM are the consequences of disruptions in homeostasis, the relationship between them is intricate. This study sought to investigate the potential influence of DM on lung cancer by employing total-body dynamic PET imaging. The present study proposes a framework for metabolic network analysis using total-body dynamic PET imaging of 20 lung cancer patients with DM (DM group) and 20 lung cancer patients without DM (Non-DM group), with the residuals of a third-order polynomial fit serving as an indicator of Pearson correlation. The framework successfully captured the deviation of the DM group from the Non-DM group at both the edge and organ levels. At the edge level, there was a significant difference in the lesion- left ventricle (LV) between the DM and Non-DM groups (P < 0.05). Furthermore, we discovered a positive correlation between the absolute value of Z-score (ZCC) of lesion - LV and the duration of DM (R = 0.680, P < 0.001). At the organ level, there was a significant difference in the kidney, brain, and abdominal fat between the DM and Non-DM groups (P < 0.05). This study demonstrated the feasibility of constructing metabolic networks to uncover complex alterations in lung cancer patients with DM. The findings contribute to understanding the systemic effects of DM on lung cancer metabolism and highlight the importance of personalized metabolic network analysis to comprehend the implications of concurrent diseases.

Long-range PCR as a tool for evaluating mitochondrial DNA damage: Principles, benefits, and limitations of the technique.

Mitochondrial DNA (mtDNA) is often more susceptible to damage compared to nuclear DNA. This is due to its localization in the mitochondrial matrix, where a large portion of reactive oxygen species are produced. Mitochondria do not have histones and mtDNA is only slightly protected by histone-like proteins and is believed to have less efficient repair mechanisms. In this review, we discuss the long-range PCR method, which allows for the effective detection of mtDNA damage. The method is based on the assumption that various types of DNA lesions can interfere the progress of DNA polymerase, resulting in reduced amplification efficiency. It can be used to estimate the number of additional (above background) lesions in mtDNA. The review outlines the evolution of the methodology, its variations, applications in a wide range of model organisms, the advantages of the method and its limitations, as well as ways to overcome these limitations. Over the past two decades, the use of long-range PCR has allowed the study of mtDNA repair mechanisms, the characteristics of mitochondrial genome damage in various neurodegenerative diseases, aging, ischemic and oncological processes, as well as in anticancer therapy. The assessment of mtDNA damage has also been proposed for use in environmental biomonitoring. This review provides a critical evaluation of the various variations of this method, summarizes the accumulated data, and discusses the role of mtDNA damage in different organs at the organismal level.

Intraspecific Morphometric Variation in a New Species of Ceratomyxa Thélohan 1892 (Cnidaria) from the South Atlantic Ocean: An Ecomorphological Study Using Geometric Morphometrics.

A new species of Ceratomyxa (Ceratomyxidae, Myxosporea) was found infecting the gall bladder of the Argentine croaker Umbrina canosai Berg 1895 (Sciaenidae, Perciformes) from the Argentine sea. Using an integrative taxonomic approach that combines morphological, bioecological, and molecular analyses, we provide evidence that clearly differentiates this species from known taxa and formally describe Ceratomyxa fialai as a new species. This study is the first to apply landmark-based geometric morphometrics (GM) in myxozoan research, providing a detailed analysis of conspecific morphometric variation of ceratomyxid myxospores, examining their natural variation within and among different ceratomyxids infecting the gall bladder of U. canosai. Using GM analyses, we successfully capture and quantify phenotypic variation at the organismal level. Our results suggest that myxospore shape variation may be driven by both developmental noise and phenotypic plasticity. The work highlights the utility of GM in advancing the understanding of myxozoan morphology and its evolutionary implications and emphasizes the need for further research on myxospore shape evolution and its ecological and adaptive significance in natural populations.

Mammalian Lactation as a Framework for Teaching Development, Physiology, and Cell Biology for Social Change.

Mammalian lactation is a dynamic process that develops throughout the lifespan of an organism. Here we present a framework for a third semester core course in biology that centers course content on lactation allowing examination of the developmental process as a dynamic whole-body experience involving changes occurring at the molecular, cellular, and organ levels of organization. Inequitable economic, socio- and geopolitical systems structure social determinants of health, affecting rates of breastfeeding in human populations. By integrating content exploring the ways social and biological systems impact breastfeeding rates in human populations, students develop abilities to understand the relationship between science and society throughout the course, a critical core competency for engaging in social change. Importantly, they interrogate social systems while simultaneously learning about many canonical biological processes including how natural selection and constraint have shaped the anatomy, physiology, cell biology, and biochemistry of lactation, how proteins, lipids, and carbohydrates are synthesized, processed, and exported through the endomembrane system in eukaryotes, and how neuronal and hormonal feedback mechanisms regulate milk synthesis and secretion. The course is structured using a flipped-classroom design emphasizing revision and student-self assessment that supports development of biological knowledge, social responsibility, and metacognitive skills. Because mammalian lactation includes fascinating, nuanced, and complex components that cross interdisciplinary boundaries, it provides a wealth of opportunities for faculty to teach developmental biology for social change.

On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations.

A transport protein's turnover rate (TOR) is the maximum rate of substrate translocation under saturating conditions. This parameter represents the number of transporting events per transporter molecule (assuming a single transport site) per second (s). From this standpoint, a transporter's TOR is similar to an enzyme's catalytic constant. Knowledge of a transporter's TOR allows comparison of the transport capacity of various transporters at the molecular level as well as the total transport per cell and whole organ levels. Despite this, there is currently a very limited number of transporters, for which TOR has been determined experimentally. In the SLC4 transporter family of CO3 2-/HCO3 - transporters, erythrocyte AE1 (eAE1; SLC4A1) is the only member, for which TOR has been determined (∼50,000 s-1). Whether other SLC4 family members have similar TOR values is currently unknown. Here we report TOR measurements of the electrogenic Na+-CO3 2- cotransporter NBCe1-A (SLC4A4) and the kidney specific AE1 splice variant, kAE1, that play important roles in renal bicarbonate absorption and are mutated in proximal and distal renal tubular acidosis respectively. We have also remeasured the eAE1 TOR value for comparison. NBCe1-A had a TOR value of ∼30,400 s-1 whereas kAE1 and eAE1 had significantly higher values (62,000 s-1 and 60,500 s-1 respectively). We modeled the inward-facing (IF) conformation of NBCe1-A to determine conformational changes during its transport cycle. Comparison of this IF model with our previously determined cryoelectron microscopy (cryoEM) outward-facing (OF) conformation structure, demonstrates that NBCe1-A has an elevator-type transport mechanism with a small vertical ∼5 Å shift of the ion coordination site as we have previously shown for AE1. We speculate that this very small vertical movement plays an important role in contributing to the very high TOR numbers of SLC4 transporters.

Potential Health Risks of Exposure to Graphene and Its Derivatives: A Review

Graphene and its derivatives (GDs) have been applied in many fields, like photocatalysts, sensors, and biomedical delivery, due to its excellent physicochemical properties. However, the widespread use of GDs has significantly increased human exposure to these materials. Some health risks of exposure to GDs have been identified, including organ fibrosis, inflammation, DNA damage, etc. Given that graphene is a novel concern, we especially emphasized the various exposure pathways and potential health risks of exposure to GDs. People get exposed to GDs mainly through inhalation, ingestion, dermal contact, etc. GDs could transfer to the circular system of people and accumulate in blood, cells, and major organs. GDs exposure could induce organ and cell inflammatory responses and damage, such as disrupted kidney function, declined cell vitality, cytotoxicity, etc. These changes at the organ and cell levels might lead to adverse tangible influences on people, like decreased locomotor activity, the accelerated aging process, and even abnormal offspring development. We also summarized the characterization and detection methods of GDs. In addition, we compared the studies of exposure to dust and GDs in the aspects of health risks and study methods. This review could offer a comprehensive summary related to GDs and provide helpful references for further graphene-related studies.

Multimodal Study of Murine Cardiovascular Remodeling: Four-Dimensional Ultrasound and Mass Spectrometry Imaging.

Cardiovascular disease (CVD) is the leading cause of death in the United States. Damage inthe cardiovascular system can be due to environmental exposure, trauma, drug toxicity, or numerous other factors.As a result, cardiac tissue and vasculature undergo structural changes and display diminished function. The damage and the resulting remodeling can be detected and quantified with ultrasound (US) imaging at the organ level and mass spectrometry imaging (MSI) at the molecular level. This manuscript describes an innovative methodology for studying murine cardiac pathophysiology, coupling in vivo four-dimensional (4D) ultrasound imaging and analysis with ex vivo matrix-assisted laser desorption/ionization (MADLI) MSI of the heart. 4D ultrasound can provide dynamic volumetric measurements, including radial displacement, surface area strain, and longitudinal strain throughout an entire cardiac cycle. In the vasculature, MSI and ultrasound are used to assess vessel wall compositions, hemodynamics, and vessel wall dynamics. The methodology can be tailored to study a myriad of CV diseases by adjusting functional metrics of interest and/or varying MALDI MSI protocol to target specific molecules. MALDI MSI can be used to study lipids, small metabolites, peptides, and glycans. This protocol outlines the use of MALDI MSI for untargeted lipidomic analysis and the use of ultrasound imaging for cardiovascular hemodynamics and biomechanics.

First person – Michael Koch

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models &amp; Mechanisms, helping researchers promote themselves alongside their papers. Michael Koch is first author on ‘ Dose-dependent effects of Nrf2 on the epidermis in chronic skin inflammation’, published in DMM. Michael conducted the research described in this article while a PhD candidate and research scientist in Professor Sabine Werner's lab at ETH Zürich, Zürich, Switzerland. His research interests include determining how dysregulation of complex networks on a molecular level leads to disease on an organ level, and how we can target those dysregulations to develop novel therapeutic approaches.

Hormone Signaling in Breast Development and Cancer.

Hormones control normal breast development and function. They also impinge on breast cancer (BC) development and disease progression in direct and indirect ways. The major ovarian hormones, estrogens and progesterone, have long been established as key regulators of mammary gland development in rodents and linked to human disease. However, their roles have been difficult to disentangle because they act on multiple tissues and can act directly and indirectly on different cell types in the breast, and their receptors interact at different levels within the target cell. Estrogens are well-recognized drivers of estrogen receptor-positive (ER+) breast cancers, and the ER is successfully targeted in ER+ disease. The role of progesterone receptor (PR) as a potential target to be activated or inhibited is debated, and androgen receptor (AR) signaling has emerged as a potentially interesting pathway to target on the stage.In this chapter, we discuss hormone signaling in normal breast development and in cancer, with a specific focus on the key sex hormones: estrogen, progesterone, and testosterone. We will highlight the complexities of endocrine control mechanisms at the organismal, tissue, cellular, and molecular levels. As we delve into the mechanisms of action of hormone receptors, their interplay and their context-dependent roles in breast cancer will be discussed. Drawing insights from new preclinical models, we will describe the lessons learned and the current challenges in understanding hormone action in breast cancer.

Plastic pollution and marine mussels: Unravelling disparities in research efforts, biological effects and influences of global warming.

The ever-growing contamination of the environment by plastics is a major scientific and societal concern. Specifically, the study of microplastics (1μm to 5mm), nanoplastics (< 1μm), and their leachates is a critical research area as they have the potential to cause detrimental effects, especially when they impact key ecological species. Marine mussels, as ecosystem engineers and filter feeders, are particularly vulnerable to this type of pollution. In this study, we reviewed the 106 articles that focus on the impacts of plastic pollution on marine mussels. First, we examined the research efforts in terms of plastic characteristics (size, polymer, shape, and leachates) and exposure conditions (concentration, duration, species, life stages, and internal factors), their disparities, and their environmental relevance. Then, we provided an overview of the effects of plastics on mussels at each organisational levels, from the smaller scales (molecular, cellular, tissue and organ impacts) to the organism level (functional, physiological, and behavioural impacts) as well as larger-scale implications (associated community impacts). We finally discussed the limited research available on multi-stressor studies involving plastics, particularly in relation to temperature stress. We identified temperature as an underestimated factor that could shape the impacts of plastics, and proposed a roadmap for future research to address their combined effects. This review also highlights the impact of plastic pollution on mussels at multiple levels and emphasises the strong disparities in research effort and the need for more holistic research, notably through the consideration of multiple stressors, with a specific focus on temperature which is likely to become an increasingly relevant forcing factor in an era of global warming. By identifying critical gaps in current knowledge, we advocate for more coordinated interdisciplinary and international collaborations and raise awareness of the need for environmental coherence in the choice and implementation of experimental protocols.

Impact of biotic and abiotic factors on epibiotic communities of the Barents Sea red king crab

Based on a long-term dataset of species composition and infestation levels of associated organisms on the invasive Barents Sea red king crab, a multivariate analysis was conducted to determine the contributions of biotic and abiotic factors to the fouling community structure. Results indicate that host size and exoskeleton age were the most significant factors for diversity indices and infestation intensity. Abiotic factors played a diminished role in the formation of fouling communities. Temperature conditions during the mass molting periods were found to have significant effects, apparently serving as a catalyst for the primary settlement of crab shells by benthic organisms. Our data not only yield new insights into the formation of fouling communities of decapod crustaceans, but also provide valuable information for further studies on the adaptation process of the red crab to the conditions of the Barents Sea.

Adipose tissue as target of environmental toxicants: focus on mitochondrial dysfunction and oxidative inflammation in metabolic dysfunction-associated steatotic liver disease.

Obesity, diabetes, and their cardiovascular and hepatic comorbidities are alarming public health issues of the twenty-first century, which share mitochondrial dysfunction, oxidative stress, and chronic inflammation as common pathophysiological mechanisms. An increasing body of evidence links the combined exposure to multiple environmental toxicants with the occurrence and severity of metabolic diseases. Endocrine disruptors (EDs) are ubiquitous chemicals or mixtures with persistent deleterious effects on the living organisms beyond the endocrine system impairment; in particular, those known as metabolism-disrupting chemicals (MDCs), increase the risk of the metabolic pathologies in adult organism or its progeny. Being largely lipophilic, MDCs mainly target the adipose tissue and elicit mitochondrial dysfunction by interfering with mitochondrial bioenergetics, biogenesis, dynamics and/or other functions. Plastics, when broken down into micro- and nano-plastics (MNPs), have been detected in several human tissues, including the liver. The harmful interplay between inflammatory and redox processes, which mutually interact in a positive feed-back loop, hence the term oxidative inflammation ("OxInflammation"), occurs both at systemic and organ level. In both liver and adipose tissue, oxinflammation contributes to the progression of the metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, it has been reported that individuals with MASLD may be more susceptible to the harmful effects of toxicants (mainly, those related to mitochondria) and that chronic exposure to EDs/MDCs or MNPs may play a role in the development of the disease. While liver has been systematically investigated as major target organ for ambient chemicals, surprisingly, less information is available in the literature with respect to the adipose tissue. In this narrative review, we delve into the current literature on the most studied environmental toxicants (bisphenols, polychlorinated biphenyls, phthalates, tolylfluanid and tributyltin, per-fluoroalkyl and polyfluoroalkyl substances, heavy metals and MNPs), summarize their deleterious effects on adipose tissue, and address the role of dysregulated mitochondria and oxinflammation, particularly in the setting of MASLD.

Using Relational Biology with Loop Analysis to Study the North Atlantic Biological Carbon Pump in a ‘Hybrid’ Non-Algorithmic Manner

Biologists, philosophers, and mathematicians building upon Robert Rosen’s non-algorithmic theories of life using Relational Biology and Category Theory have continued to develop his theory and modeling approaches. There has been general agreement that the impredicative, self-referential, and complex nature of living systems negates an algorithmic approach. Rosen’s main goal was to answer, “What is Life?”. Many believe he provided the best but minimum answer using a cellular, metabolism–repair or (M, R)-system as a category-theoretic model. It has been challenging, however, to incorporate his theory to develop a fully non-algorithmic methodology that retains the essence of his thinking while creating more operational models of living systems that can be used to explore other facets of life and answer different questions. Living systems do more than the minimum in the real world beyond the confines of definition alone. For example, ecologists ask how living systems inherently mitigate existential risk from climate change and biodiversity loss through their complex self-organization. Loop Analysis, a signed graph technique, is discussed as a hybrid algorithmic/non-algorithmic methodology in Relational Biology. This methodology can be used at the ecosystem level with standard non-algorithmic field data as per McAllister’s description of the algorithmic incompressibility of empirical data of this type. An example is described showing how the North Atlantic Carbon Pump, an important planetary life support system, is situated in the plankton community and functions as a mutualistic ecosystem chimera. It captures carbon from the atmosphere as an extended (M, R)-system and processes it until it is sequestered in the marine sediments. This is an important process to alleviate climate change in magnitude equal to or larger than the sequestration of carbon on land with forests. It is suggested that the ecosystem level should replace the cellular and organismic levels as the main system unit in biology and evolution since all life exists and evolves with full functional potential in ecosystem networks and not laboratory test tubes. The plankton ecosystem is the largest after the total biosphere and consists of evolutionary links and relationships that have existed for eons of time. If there was ever a genuine robust, highly self-organized ecosystem, it would be planktonic. Severing the links in these thermodynamically open networks by focusing on lower levels of the biological hierarchy loses the critical organization of how life exists on this planet. There is no theory to regain this crucial ‘omitted’ ecological relational causality at the cell or organismal levels. At the end of the paper, some future directions are outlined.

Species- and organ-specific contribution of peroxisomal cinnamate:CoA ligases to benzoic and salicylic acid biosynthesis.

Salicylic acid (SA) is a prominent defense hormone whose basal level, organ-specific accumulation, and physiological role vary widely among plant species. Of the two known pathways of plant SA biosynthesis, the phenylalanine ammonia lyase (PAL) pathway is more ancient and universal but its biosynthetic and physiological roles in diverse plant species remain unclear. Studies in which the PAL pathway is specifically or completely inhibited, as well as a direct comparison of diverse species and different organs within the same species, are needed. To this end, we analyzed the PAL pathway in rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), two distantly related model plants whose basal SA levels and distributions differ tremendously at the organism and tissue levels. Based on our recent identification of the rice peroxisomal cinnamate:CoA ligases (CNLs), we identified two peroxisomal CNLs from Arabidopsis and showed CNL as the most functionally specific enzyme among the known enzymes of the PAL pathway. We then revealed the species- and organ-specific contribution of the PAL pathway to benzoic and salicylic acid biosynthesis and clarified its physiological importance in rice and Arabidopsis. Our findings highlight the necessity to consider species and organ types in future SA-related studies and may help to breed new disease-resistant crops.

A complex systems approach to mosaic loss of the Y chromosome.

Mosaic loss of Y chromosome (mLOY) is an acquired condition wherein a sizeable proportion of an organ's cells have lost their Y. Large-scale cohort studies have shown that mLOY is age-dependent and a strong risk factor for all-cause mortality and adverse outcomes of age-related diseases. Emerging multi-omics approaches that combine gene expression, epigenetic and mutational profiling of human LOY cell populations at single-cell levels, and contemporary work in in vitro cell and preclinical mouse models have provided important clues into how mLOY mechanistically contributes to disease onset and progression. Despite these advances, what has been missing is a system-level insight into mLOY. By integrating the most recent advances in wide-ranging aspects of mLOY research, we summarize a unified model to understanding the cause and consequence of mLOY at the molecular, cellular, and organismal levels. This model, referred to as the "Unstable Y Cascade model," states that (i) the rise and expansion of LOY result from interaction by the inherently unstable Y, germline genetic and epigenetic variants, and numerous cell-intrinsic and external factors; (ii) LOY initiates genomic, epigenomic, and transcriptomic alterations in X and autosomes, thereafter induces a cascade of tissue-specific cellular alterations that contribute locally to the onset and progression of diseases; and (iii) LOY cells exert paracrine effects to non-LOY cells, thereby amplifying LOY-associated pathological signaling cascades to remote non-LOY cells. This new model has implications in the development of therapeutic interventions that could prevent or delay age-related diseases via mitigating mLOY burden.

Organ-on-a-Chip Models-New Possibilities in Experimental Science and Disease Modeling.

'Organ-on-a-chip' technology is a promising and rapidly evolving model in biological research. This innovative microfluidic cell culture device was created using a microchip with continuously perfused chambers, populated by living cells arranged to replicate physiological processes at the tissue and organ levels. By consolidating multicellular structures, tissue-tissue interfaces, and physicochemical microenvironments, these microchips can replicate key organ functions. They also enable the high-resolution, real-time imaging and analysis of the biochemical, genetic, and metabolic activities of living cells in the functional tissue and organ contexts. This technology can accelerate research into tissue development, organ physiology and disease etiology, therapeutic approaches, and drug testing. It enables the replication of entire organ functions (e.g., liver-on-a-chip, hypothalamus-pituitary-on-a-chip) or the creation of disease models (e.g., amyotrophic lateral sclerosis-on-a-chip, Parkinson's disease-on-a-chip) using specialized microchips and combining them into an integrated functional system. This technology allows for a significant reduction in the number of animals used in experiments, high reproducibility of results, and the possibility of simultaneous use of multiple cell types in a single model. However, its application requires specialized equipment, advanced expertise, and currently incurs high costs. Additionally, achieving the level of standardization needed for commercialization remains a challenge at this stage of development.

Bioassays with Allium cepa for the Monitoring of Toxicity in the Groundwater of Yucatan, Mexico

This study employed the Allium cepa bioassay to evaluate the toxic effects of contaminants in the Yucatan aquifer. Seven monitoring wells were studied during September and October 2021. Nutrient concentrations showed significant variation between sites, with samples closer to the coast (P3 and P7) presenting higher ammonia and phosphate concentrations. The pesticides found at the highest concentration were δ-HCH and chlorpyrifos, with 141.44 and 175.92 ng/L, respectively. Heptachlor and aldrin were present in sites P4oct and P2sept. Interestingly, DDT values were highly correlated with caffeine concentrations. The PAHs acenaphthylene and the sum of B(k)fluoranthene and B(b)fluoranthene presented the highest prevalence. B(k)fluoranthene and B(b)fluoranthene were the PAHs found at the highest concentration. The results of the A. cepa bioassay indicated no nuclear abnormalities. The study also found no statistical differences in the mitotic index, root length, biomarkers of oxidative stress, and inhibition of B-esterases between sites and controls. In summary, the wells sampled in the present study had low concentrations of contaminants that can be used as a proxy of anthropogenic discharges; the lack of effect in the biomarkers used at organism, cellular, and biochemical levels indicated no toxic effect on A. cepa roots.

Combining Cold Atmospheric Plasma and Environmental Nanoparticle Removal Device Reduces Neurodegenerative Markers.

Ageing leads to a gradual deterioration of the organs, with the brain being particularly susceptible, often leading to neurodegeneration. This process includes well-known changes such as tau hyperphosphorylation and beta-amyloid deposition, which are commonly associated with neurodegenerative diseases but are also present in ageing. These structures are triggered by earlier cellular changes such as energy depletion and impaired protein synthesis, both of which are essential for cell function. These changes may in part be induced by environmental pollution, which has been shown to accelerate these processes. Cold Atmospheric Plasma (CAP) or atmospheric pressure gas discharge plasmas have shown promise in activating the immune system and improving cellular function in vitro, although their effects at the organ level remain poorly understood. Our aim in this work is to investigate the effect of a device that combines CAP treatment with the effective removal of environmental nanoparticles, typical products of pollution, on the activity of aged mouse brains. The results showed an increase in energy capacity, a reduction in reticulum stress and an activation of cellular autophagic clearance, minimising aggresomes in the brain. This leads to a reduction in key markers of neurodegeneration such as tau hyperphosphorylation and beta-amyloid deposition, demonstrating the efficacy of the tested product at the brain level.