Metabolic Waste Products Research Articles

Structural characterization and anti-fatigue mechanism based on the gut-muscle axis of a polysaccharide from Zingiber officinale

This study aimed to characterize the structure of polysaccharide ZOPA extracted from Zingiber officinale and its purified form (ZOPA-1), and to investigate their anti-fatigue mechanisms based on the gut-muscle axis. The study found that the backbone of ZOPA-1 is primarily composed of →3,4)-α-Glcp-1→ and →4,6)-α-Glcp-(1→ linkages, with →4)-α-Glcp(1→ serving as its side chain. In exhaustive swimming experiments with mice, both crude ZOPA and purified ZOPA-1 demonstrated significant anti-fatigue effects, including enhanced glycogen storage, improved antioxidant capacity, reduced accumulation of metabolic waste products, and regulated energy metabolism in the gastrocnemius muscles. These effects may be mediated through the activation of the Keap1-Nrf2/ARE and AMPK/PGC-1α signaling pathways. Furthermore, ZOPA and ZOPA-1 modulated the intestinal flora of mice, increasing diversity, altering abundance, and regulating short-chain fatty acid concentrations, suggesting a potential role of the gut-muscle axis in mediating the anti-fatigue effects. This study provides valuable insights into the complex interplay between polysaccharides, the gut-muscle axis, and exercise-induced fatigue.

A new era in the treatment of kidney diseases: NLRP3 inflammasome and cytokine-targeted therapies.

The kidneys are crucial for filtering blood, managing overall body water, electrolyte, and acid-base balance, and regulating blood pressure. They remove metabolic waste products, toxins, and drugs. In addition, they limit inflammation by clearing cytokines and reduce immune cell activation by removing bacterial components. Dendritic cells (DCs) in the kidney maintain peripheral tolerance. About 85% of filtered water is reabsorbed by the proximal tubule, exposing distal nephron cells to high concentrations of low molecular weight antigens. These antigens are captured by DCs, helping to inactivate potentially autoreactive T cells and maintain tolerance to circulating antigens. In kidney failure, immune function is severely compromised due to the retention of toxins and cytokines, which activate immune cells and increase systemic inflammation. The kidneys are also vulnerable to immune-mediated diseases. Loss of immune homeostasis, characterized by over- or under-activity of the immune response, can adversely affect kidney function. With advances in immunology and cellular biology, biologic therapies targeting various pathways involved in the pathophysiology of kidney diseases are being developed. In this review, the immunologic aspects of kidney diseases and focus on cytokine-based therapies that may hold promise for the treatment of kidney diseases in the future will be presented.

A Macrocyclic Hybrid PET/MRI Probe for Quantitative Perfusion Imaging In Vivo.

Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction, a condition that is typically challenging to diagnose. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for practical synthesis and improved diagnostic accuracy.

Parasagittal dural volume correlates with cerebrospinal fluid volume and developmental delay in children with autism spectrum disorder

BackgroundThe parasagittal dura, a tissue that lines the walls of the superior sagittal sinus, acts as an active site for immune-surveillance, promotes the reabsorption of cerebrospinal fluid, and facilitates the removal of metabolic waste products from the brain. Cerebrospinal fluid is important for the distribution of growth factors that signal immature neurons to proliferate and migrate. Autism spectrum disorder is characterized by altered cerebrospinal fluid dynamics.MethodsIn this retrospective study, we investigated potential correlations between parasagittal dura volume, brain structure volumes, and clinical severity scales in young children with autism spectrum disorder. We employed a semi-supervised two step pipeline to extract parasagittal dura volume from 3D-T2 Fluid Attenuated Inversion Recovery sequences, based on U-Net followed by manual refinement of the extracted parasagittal dura masks.ResultsHere we show that the parasagittal dura volume does not change with age but is significantly correlated with cerebrospinal fluid (p-value = 0.002), extra-axial cerebrospinal fluid volume (p-value = 0.0003) and severity of developmental delay (p-value = 0.024).ConclusionsThese findings suggest that autism spectrum disorder children with severe developmental delay may have a maldeveloped parasagittal dura that potentially perturbs cerebrospinal fluid dynamics.

Molecular basis of the urate transporter URAT1 inhibition by gout drugs.

Hyperuricemia is a condition when uric acid, a waste product of purine metabolism, accumulates in the blood1. Untreated hyperuricemia can lead to crystal formation of monosodium urate in the joints, causing a painful inflammatory disease known as gout. These conditions are associated with many other diseases and affect a significant and increasing proportion of the population2-4. The human urate transporter 1 (URAT1) is responsible for the reabsorption of ~90% of uric acid in the kidneys back into the blood, making it a primary target for treating hyperuricemia and gout5. Despite decades of research and development, clinically available URAT1 inhibitors have limitations because the molecular basis of URAT1 inhibition by gout drugs remains unknown5. Here we present cryo-electron microscopy structures of URAT1 alone and in complex with three clinically relevant inhibitors: benzbromarone, lesinurad, and the novel compound TD-3. Together with functional experiments and molecular dynamics simulations, we reveal that these inhibitors bind selectively to URAT1 in inward-open states. Furthermore, we discover differences in the inhibitor dependent URAT1 conformations as well as interaction networks, which contribute to drug specificity. Our findings illuminate a general theme for URAT1 inhibition, paving the way for the design of next-generation URAT1 inhibitors in the treatment of gout and hyperuricemia.

Research Progress in the Construction and Application of In Vitro Vascular Models

The vascular system maintains cellular homeostasis by transporting oxygen, nutrients, and metabolic waste products. The vascular system is involved in a variety of fundamental physiological phenomena and is closely associated with human vascular diseases. Additionally, the stability of drugs in the vasculature affects their efficacy. Therefore, researchers have used vascular models to study vascular diseases, assess drug stability, and screen drugs. However, there are many shortcomings in the animal models and in vitro two-dimensional vascular models that have been extensively developed. In this paper, we specifically review the construction methods of in vitro vascular models and classify the specific methods into photolithography, soft lithography, self-assembly, template, 3D bioprinting, and laser degradation/cavitation. The first two are microfluidics-based methods and the last three are non-microfluidics-based methods. The vascular model construction methods reviewed in this paper overcome the shortcomings of traditional models—which cannot accurately reproduce the human vascular microenvironment—and can assist in the construction of in vitro 3D vascular models and tissue engineering vascularization. These models can be reused by perfusion devices, and the cells within the channels reside on biocompatible materials that are used to simulate the microenvironment and 3D cellular organization of the vasculature in vivo. In addition, these models are reproducible in shape and length, allowing experiments to be repeated, which is difficult to do with natural vessels. In vitro vascular models are widely used in research and drug screening for diseases associated with endothelial dysfunction, cancer, and other vascular abnormalities.

Primaquine-5,6-Orthoquinone Is Directly Hemolytic to Older G6PD Deficient RBCs in a Humanized Mouse Model.

Primaquine and Tafenoquine are the only approved drugs that can achieve a radical cure for Plasmodium vivax malaria but are contraindicated in patients who are deficient in glucose 6-phosphate dehydrogenase (G6PDd) due to risk of severe hemolysis from reactive oxygen species generated by redox cycling of drug metabolites. 5-hydroxyprimaquine and its quinoneimine cause robust redox cycling in red blood cells (RBCs) but are so labile as to not be detected in blood or urine. Rather, the quinoneimine is rapidly converted into primaquine-5,6-orthoquinone (5,6-POQ) that is then excreted in the urine. The extent to which 5,6-POQ contributes to hemolysis remains unclear, although some have suggested that it is a minor toxin that should be used predominantly as a surrogate to infer levels of 5-hydroxyprimaquine. In this report, we describe a novel humanized mouse model of the G6PD Mediterranean variant (hG6PDMed-) that recapitulates the human biology of RBC age-dependent enzyme decay, as well as an isogenic matched control mouse with human nondeficient G6PD hG6PDND In vitro challenge of RBCs with 5,6-POQ causes increased generation of superoxide and methemoglobin. Infusion of treated RBCs shows that 5,6-POQ selectively causes in vivo clearance of older hG6PDMed- RBCs. These findings support the hypothesis that 5,6-POQ directly induces hemolysis and challenges the notion that 5,6-POQ is an inactive metabolic waste product. Indeed, given the extreme lability of 5-hydroxyprimaquine and the relative stability of 5,6-POQ, these data raise the possibility that 5,6-POQ is a major hemolytic primaquine metabolite in vivo. SIGNIFICANCE STATEMENT: These findings demonstrate that 5,6-POQ, which has been considered an inert waste product of primaquine metabolism, directly induces ROS that cause clearance of older G6PDd RBCs. As 5,6-POQ is relatively stable compared with other active primaquine metabolites, these data support the hypothesis that 5,6-POQ is a major toxin in primaquine induced hemolysis. The findings herein also establish a new model of G6PDd and provide the first direct evidence, to our knowledge, that young G6PDd RBCs are resistant to primaquine-induced hemolysis.

The history context and future directions of lactic acid

Lactic acid, initially considered a neglected metabolic waste product, has gradually shown its irreplaceable value in the human body. Up to now, it has become a hot topic of current research. From its first time its discovery in milk to its becoming a product of cellular respiration and metabolism, lactic acid was viewed to be a useless product in metabolism and therefore resulted in the suspension of related research. Later, with the birth of the concept of lactate shuttle between cells, lactate once again showed a very important function in the energy field of physiological research, including the participation of whole-body energy metabolism and the regulation of the cancer microenvironment. However, after some time, the research on lactic acid seems to have stalled again in the role of lactic acid as a small molecule. Not until 2019, the discovery of acetylation of histone extended a new field of lactate research epigenetic modification. This review summarizes the research on various aspects of lactate and highlights the progress and application of lactate in histone modification.

Oxidative stress and plasma ceramides in broiler chickens.

The selection for rapid growth in chickens has rendered meat-type (broiler) chickens susceptible to develop metabolic syndrome and thus inflammation. The sphingolipid ceramide has been linked as a marker of oxidative stress in mammals, however, the relationship between sphingolipid ceramide supply and oxidative stress in broiler chickens has not been investigated. Therefore, we employed a lipidomic approach to investigate the changes in circulating sphingolipid ceramides in context of allopurinol-induced oxidative stress in birds. Day zero hatched chicks (n = 60) were equally divided into six groups; an unsupplemented control, an allopurinol group (25mg/kg body weight), a conjugated linoleic acid (CLA) group where half of the oil used in the control diet was substituted for a CLA oil mixture, a CLA and an allopurinol group utilizing the same dose of CLA and allopurinol, a berberine (BRB) group consisting of berberine supplementation (200mg/kg feed), and a BRB and allopurinol group, utilizing the same dose of BRB and allopurinol. Conjugated linoleic acid and berberine were utilized to potentially enhance antioxidant activity and suppress the oxidative stress induced by allopurinol treatment. Body weight, plasma uric acid, nonesterified fatty acids (NEFA) and sphingolipid ceramides were quantified. Allopurinol induced an inflammatory state as measured by a significant reduction in plasma uric acid - an antioxidant in birds as well as a metabolic waste product. Results showed that both total and saturated sphingolipid ceramides declined (p < 0.05) with age in unsupplemented chicks, although plasma ceramides C16:0 and 18:0 increased in concentration over the study period. Simple total and saturated sphingolipid ceremide's were further decreased (p < 0.05) with allopurinol supplementation, however, this may be an indirect consequence of inducing an inflammatory state. Neither CLA or BRB were able to significantly attenuate the decline. The administration of allopurinol specifically targets the liver which in birds, is the primary organ for fatty acids synthesis. For this reason, sphingolipid ceramide production might have been unwittingly affected by the addition of allopurinol.

The Multiple Roles of Lactate in the Skeletal Muscle.

Believed for a long time to be merely a waste product of cell metabolism, lactate is now considered a molecule with several roles, having metabolic and signalling functions together with a new, recently discovered role as an epigenetic modulator. Lactate produced by the skeletal muscle during physical exercise is conducted to the liver, which uses the metabolite as a gluconeogenic precursor, thus generating the well-known "Cori cycle". Moreover, the presence of lactate in the mitochondria associated with the lactate oxidation complex has become increasingly clear over the years. The signalling role of lactate occurs through binding with the GPR81 receptor, which triggers the typical signalling cascade of the G-protein-coupled receptors. Recently, it has been demonstrated that lactate regulates chromatin state and gene transcription by binding to histones. This review aims to describe the different roles of lactate in skeletal muscle, in both healthy and pathological conditions, and to highlight how lactate can influence muscle regeneration by acting directly on satellite cells.

Role of lactate and lactate metabolism in liver diseases (Review).

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Unveiling Selected Influences on Chronic Kidney Disease Development and Progression.

Currently, more and more people are suffering from chronic kidney disease (CKD). It is estimated that CKD affects over 10% of the population worldwide. This is a significant issue, as the kidneys largely contribute to maintaining homeostasis by, among other things, regulating blood pressure, the pH of blood, and the water-electrolyte balance and by eliminating unnecessary metabolic waste products from blood. What is more, this disease does not show any specific symptoms at the beginning. The development of CKD is predisposed by certain conditions, such as diabetes mellitus or hypertension. However, these disorders are not the only factors promoting the onset and progression of CKD. The primary purpose of this review is to examine renin-angiotensin-aldosterone system (RAAS) activity, transforming growth factor-β1 (TGF-β1), vascular calcification (VC), uremic toxins, and hypertension in the context of their impact on the occurrence and the course of CKD. We firmly believe that a deeper comprehension of the cellular and molecular mechanisms underlying CKD can lead to an enhanced understanding of the disease. In the future, this may result in the development of medications targeting specific mechanisms involved in the decline of kidney function. Our paper unveils the selected processes responsible for the deterioration of renal filtration abilities.

Microglia lactylation in relation to central nervous system diseases.

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis. Microglia, as innate immune cells, play important roles in the maintenance of central nervous system homeostasis, injury response, and neurodegenerative diseases. Lactate has been considered a metabolic waste product, but recent studies are revealing ever more of the physiological functions of lactate. Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions, macrophage polarization, neuromodulation, and angiogenesis and has also been implicated in the development of various diseases. This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation, histone versus non-histone lactylation, and therapeutic approaches targeting lactate. Finally, we summarize the current research on microglia lactylation in central nervous system diseases. A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Metabolic pathways of glucose and fructose: II Spatiotemporal expression of genes involved in synthesis and transport of lactate in ovine conceptuses†.

Lactate, an abundant molecule in fetal fluids and blood of mammalian species, is often overlooked as a metabolic waste product generated during pregnancy. Most of the glucose and fructose consumed by ovine conceptuses is converted to lactate, but proteins involved in lactate metabolism and transport have not been investigated. This study characterized total lactate produced by ovine conceptuses throughout gestation, as well as expression of mRNAs and proteins involved in lactate metabolism. Lactate increased in abundance in the uterine lumen during the preimplantation period and was more abundant than pyruvate. The abundance of lactate in allantoic and amniotic fluids increased with advancing days of gestation and most abundant on Day 125 of pregnancy (P < 0.05). Lactate dehydrogenase subunits A (converts pyruvate to lactate) and B (converts lactate to pyruvate) were expressed by conceptuses throughout gestation. Lactate is transported via monocarboxylic acid transporters SLC16A1 and SLC16A3, both of which were expressed by the conceptus throughout gestation. Additionally, the interplacentomal chorioallantois from Day 126 expressed SLC16A1 and SLC16A3 and transported lactate across the tissue. Hydrocarboxylic acid receptor 1 (HCAR1), a receptor for lactate, was localized to the uterine luminal and superficial glandular epithelia of pregnant ewes throughout gestation and conceptus trophectoderm during the peri-implantation period of gestation. These results provide novel insights into the spatiotemporal profiles of enzymes, transporters, and receptor for lactate by ovine conceptuses throughout pregnancy.

Boron nitride nanotube-based creatinine biosensors for athlete physical condition monitoring

Monitoring creatinine levels is critical for evaluating renal function and muscular health in athletes. Creatinine is a waste product of creatine metabolism in skeletal muscle, and is filtered by the kidneys at a relatively constant rate. Elevated serum creatinine can indicate impaired kidney function, rhabdomyolysis, or skeletal muscle trauma. In athletes, creatinine levels increase after intense exertion due to muscle breakdown and myoglobin release. Abnormal creatinine signifies poor training adaptation, overtraining, or trauma. Therefore, close monitoring of creatinine in athletes provides insight into their physical condition. Current laboratory methods for measuring creatinine like Jaffe reaction and high-performance liquid chromatography are accurate but time-consuming, requiring blood sampling. Biosensors offer rapid, painless creatinine detection from small volumes, but current versions suffer from instability, use of mediators, and lack portability. Boron nitride nanotubes (BNNTs) are promising materials for electrochemical biosensing due to their structure, surface chemistry, and biocompatibility. Here, we report BNNT-based electrochemical biosensors for detecting creatinine in blood samples from athletes. BNNTs synthesized by induction thermal plasma technique were used to immobilize creatinine metabolizing enzymes. Creatinine levels were measured by chronoamperometry and compared to isotope dilution mass spectrometry. We demonstrate high sensitivity and selectivity of the BNNT biosensor with facile fabrication method and portable platform, promising for rapid creatinine monitoring in athletes. This can provide insight into muscular damage and renal function during training and competition.

Advances in the differentiation of pluripotent stem cells into vascular cells.

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.

CO2 as an engine for neurofluid flow: Exploring the coupling between vascular reactivity, brain clearance, and changes in tissue properties.

The brain relies on an effective clearance mechanism to remove metabolic waste products for the maintenance of homeostasis. Recent studies have focused on elucidating the forces that drive the motion of cerebrospinal fluid (CSF), responsible for removal of these waste products. We demonstrate that vascular responses evoked using controlled manipulations of partial pressure of carbon dioxide (PaCO2) levels, serve as an endogenous driver of CSF clearance from the brain. To demonstrate this, we retrospectively surveyed our database, which consists of brain metastases patients from whom blood oxygen level-dependent (BOLD) images were acquired during targeted hypercapnic and hyperoxic respiratory challenges. We observed a correlation between CSF inflow signal around the fourth ventricle and CO2-induced changes in cerebral blood volume. By contrast, no inflow signal was observed in response to the nonvasoactive hyperoxic stimulus, validating our measurements. Moreover, our results establish a link between the rate of the hemodynamic response (to elevated PaCO2) and peritumoral edema load, which we suspect may affect CSF flow, consequently having implications for brain clearance. Our expanded perspective on the factors involved in neurofluid flow underscores the importance of considering both cerebrovascular responses, as well as the brain mechanical properties, when evaluating CSF dynamics in the context of disease processes.

Regulation of Oxygen Tension as a Strategy to Control Chondrocytic Phenotype for Cartilage Tissue Engineering and Regeneration.

Cartilage defects and osteoarthritis are health problems which are major burdens on health care systems globally, especially in aging populations. Cartilage is a vulnerable tissue, which generally faces a progressive degenerative process when injured. This makes it the 11th most common cause of global disability. Conservative methods are used to treat the initial phases of the illness, while orthopedic management is the method used for more progressed phases. These include, for instance, arthroscopic shaving, microfracturing and mosaicplasty, and joint replacement as the final treatment. Cell-based implantation methods have also been developed. Despite reports of successful treatments, they often suffer from the non-optimal nature of chondrocyte phenotype in the repair tissue. Thus, improved strategies to control the phenotype of the regenerating cells are needed. Avascular tissue cartilage relies on diffusion for nutrients acquisition and the removal of metabolic waste products. A low oxygen content is also present in cartilage, and the chondrocytes are, in fact, well adapted to it. Therefore, this raises an idea that the regulation of oxygen tension could be a strategy to control the chondrocyte phenotype expression, important in cartilage tissue for regenerative purposes. This narrative review discusses the aspects related to oxygen tension in the metabolism and regulation of articular and growth plate chondrocytes and progenitor cell phenotypes, and the role of some microenvironmental factors as regulators of chondrocytes.

Cadmium transport by mammalian ATP-binding cassette transporters.

Cellular responses to toxic metals depend on metal accessibility to intracellular targets, reaching interaction sites, and the intracellular metal concentration, which is mainly determined by uptake pathways, binding/sequestration and efflux pathways. ATP-binding cassette (ABC) transporters are ubiquitous in the human body-usually in epithelia-and are responsible for the transfer of indispensable physiological substrates(e.g. lipids and heme), protection against potentially toxic substances, maintenance of fluid composition, and excretion of metabolic waste products. Derailed regulation and gene variants of ABC transporters culminate in a wide array of pathophysiological disease states, such as oncogenic multidrug resistance or cystic fibrosis. Cadmium (Cd) has no known physiological role in mammalians and poses a health risk due to its release into the environment as a result of industrial activities, and eventually passes into the food chain. Epithelial cells, especially within the liver, lungs, gastrointestinal tract and kidneys, are particularly susceptible to the multifaceted effects of Cd because of the plethora of uptake pathways available. Pertinent to their broad substrate spectra, ABC transporters represent a major cellular efflux pathway for Cd and Cd complexes. In this review, we summarize current knowledge concerning transport of Cd and its complexes (mainly Cd bound to glutathione) by the ABC transporters ABCB1 (P-glycoprotein, MDR1), ABCB6, ABCC1 (multidrug resistance related protein 1, MRP1), ABCC7 (cystic fibrosis transmembrane regulator, CFTR), and ABCG2 (breast cancer related protein, BCRP). Potential detoxification strategies underlying ABC transporter-mediated efflux of Cd and Cd complexesare discussed.

Diel metabolic patterns revealed by insitu transcriptome and proteome in a vertically migratory copepod.

Zooplankton undergo a diel vertical migration (DVM) which exposes them to gradients of light, temperature, oxygen, and food availability on a predictable daily schedule. Disentangling the co-varying and potentially synergistic interactions on metabolic rates has proven difficult, despite the importance of this migration for the delivery of metabolic waste products to the distinctly different daytime (deep) and nighttime (surface) habitats. This study examines the transcriptomic and proteomic profiles of the circumglobal migratory copepod, Pleuromamma xiphias, over the diel cycle. The transcriptome showed that 96% of differentially expressed genes were upregulated during the middle of the day - the period often considered to be of lowest zooplankton activity. The changes in protein abundance were more spread out over time, peaking (42% of comparisons) in the early evening. Between 9:00 and 15:00, both the transcriptome and proteome datasets showed increased expression related to chitin synthesis and degradation. Additionally, at 09:00 and 22:00, there were increases in myosin and vitellogenin proteins, potentially linked to the stress of migration and/or reproductive investment. Based on protein abundances detected, there is an inferred switch in broad metabolic processes, shifting from electron transport system in the day to glycolysis and glycogen mobilization in the afternoon/evening. These observations provide evidence of the diel impact of DVM on transcriptomic and proteomic pathways that likely influence metabolic processes and subsequent excretion products, and clarify how this behaviour results in the direct rapid transport of waste metabolites from the surface to the deep ocean.