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Background: Heart rate variability (HRV) is the change in time intervals between heart beats, reflecting the autonomic nervous system's ability to adapt to psychological and physiological demands. Slow breathing enhances parasympathetic activity, increasing HRV. Pranayama, a yoga breathing technique, affords the conscious regulation of respiration frequency. This study aimed to characterize HRV, blood pressure and peripheral oxygen saturation of basic yoga breathing slow techniques with regular yoga practitioners. Methods: In total, 45 yoga practitioners were included in the study (including 7 males, mean age of 54.04 ± 11.97 years) with varying levels of yoga experience (minimum 3 months, maximum 37 years). Participants performed three breathing conditions: baseline (control) and two yoga techniques (abdominal (adham) and complete (mahat)) breathing, each for 10 min in the supine position (i.e., savasana). For each condition, respiratory frequency, heart rate (HR), blood pressure and peripheral oxygen levels were collected. Results: The findings revealed that both abdominal and complete yoga breathing techniques promoted a decrease in respiratory frequency (p < 0.001, r = 0.61; p < 0.001, r = 0.61, respectively), and an increase in peripheral oxygen saturation (p < 0.001, r = 0.50; p < 0.001, r = 0.46, respectively), along with blood pressure decreases in all mean values, and a significant decrease in systolic pressure, considering all conditions (p = 0.034, W = 0.08). There were significant increases in standard deviation of HR during abdominal and complete yoga breathing techniques compared with the baseline (p = 0.003, r = 0.31; p < 0.001, r = 0.47, respectively), indicating enhanced parasympathetic activity. Moreover, the complete breathing technique exhibited the greatest variability in HRV measures, with several significant differences compared with abdominal breathing (standard deviation of HR, p < 0.001, r = 0.42; SD2, standard deviation of points perpendicular to the Poincaré parallel line, p < 0.003, r = 0.31; SD1/SD2, p < 0.003, r = 0.31), suggesting a more profound impact on autonomic modulation. Conclusions: simple, inexpensive and non-intrusive abdominal and complete yoga breathing techniques can effectively and momentarily enhance HRV and oxygen saturation in adults, mature adults and the elderly. [ABSTRACT FROM AUTHOR]

The thermoalkaliphile Caldalkalibacillus thermarum possesses a highly branched respiratory chain. These primarily facilitate growth at a wide range of dissolved oxygen levels. The aim of this study was to investigate the regulation of C. thermarum respiratory chain. C. thermarum was cultivated in chemostat bioreactors with a range of oxygen levels (0.25% O2–4.2% O2). Proteomic analysis unexpectedly showed that both the type I and the type II NADH dehydrogenase present are constitutive. The two terminal oxidases detected were the cytochrome c :oxygen aa 3 oxidase, whose abundance was highest at 4.2% O2. The cytochrome c :oxygen ba 3 oxidase was more abundant at most other O2 levels, but its abundance started to decline below 0.42% O2. We expected this would result in the emergence of the cytochrome c :oxygen bb 3 complex or the menaquinol:oxygen bd complex, the other two terminal oxidases of C. thermarum ; but neither was detected. Furthermore, the sodium-proton antiporter complex Mrp was downregulated under the lower oxygen levels. Normally, in alkaliphiles, this enzyme is considered crucial for sodium homeostasis. We propose that the existence of a sodium:acetate exporter decreases the requirement for Mrp under strong oxygen limitation. [ABSTRACT FROM AUTHOR]

Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptor activity, mitigate hyperthermia-induced hyperventilation. We also assessed the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (V̇E) during the heating were similar in the two trials. Moreover, when V̇E is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (38.0 ± 0.3 vs. 38.0 ± 0.4°C, P = 0.469) and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-V̇E relation (13.5 ± 14.2 vs. 15.8 ± 15.5 L/min/°C, P = 0.831). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans. NEW & NOTEWORTHY: Hyperthermia leads to hyperventilation and associated cerebral hypoperfusion, both of which may impair heat tolerance. This hyperthermia-induced hyperventilation may be mediated by peripheral chemoreceptors, which can be activated by reductions in arterial pH. However, our results suggest that sodium bicarbonate ingestion, which can increase arterial pH, is not an effective intervention in alleviating hyperthermia-induced hyperventilation and cerebral hypoperfusion in resting heated humans. [ABSTRACT FROM AUTHOR]

Copper is an essential element in the human body, involved in many physiological and metabolic functions, including coagulation, oxidative metabolism, and hormone production. The maintenance of copper homeostasis within cells is a complex procedure that is intrinsically controlled by a multitude of intricate mechanisms. Disorders of copper homeostasis encompass a wide range of pathological conditions, including degenerative neurological diseases, metabolic disorders, cardio-cerebrovascular diseases, and tumors. Cuproptosis, a recently identified non-apoptotic mode of cell death mode, is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis represents a novel form of cell death distinct from the previously described modes, including apoptosis, necrosis, pyroptosis, and ferroptosis. Excess copper has been shown to induce cuproptosis by stimulating protein toxic stress responses via copper-dependent abnormal oligomerization of lipoylation proteins within the tricarboxylic acid cycle and the subsequent reduction of iron-sulfur cluster protein levels. Ferredoxin1 facilitates the lipoacylation of dihydrolipoyl transacetylase, which in turn degrades iron-sulfur cluster proteins by reducing Cu2+ to Cu+, thereby inducing cell death. Furthermore, copper homeostasis is regulated by the copper transporter, and disturbances in this homeostasis result in cuproptosis. Current evidence suggests that cuproptosis plays an important role in the onset and development of several cardiovascular diseases. Copper-chelating agents, including ammonium tetrathiomolybdate (VI) and DL-penicillamine, have been shown to facilitate the alleviation of cardiovascular disease by inhibiting cuproptosis. It is hypothesized that oxidative phosphorylation inhibitors such as physical training may inhibit cuproptosis by inhibiting the protein stress response. In conclusion, the implementation of physical training may be a viable strategy to reducte the incidence of cuproptosis. [ABSTRACT FROM AUTHOR]

This article provides an overview of the development of Scandinavian exercise physiology, with a focus on the years between 1910 and 1920 and the subsequent establishment of the Rockefeller Institute in Copenhagen in 1928. Three scientists, Erik Hohwü Christensen, Marius Nielsen, and Erling Asmussen, played key roles in advancing the field during this time. Their research centered on the adaptative resetting of homeostasis across organ systems during exercise. The article also mentions the League of Nations' Health Organization's support for a research program investigating physiological responses to maximum muscular effort, which further bolstered the work of Hohwü and Nielsen. The text goes on to discuss the collaborative efforts of Hohwü, Nielsen, and Asmussen in the 1930s and 1940s, where they conducted experiments to understand the mechanisms behind the increase in cardiac output during exercise. Their studies revealed that cardiovascular function, ventilation, and thermoregulation are tightly regulated during exercise, with feedback mechanisms originating within the working skeletal muscle. Additionally, they identified a neural feedback mechanism related to the volume of involved musculature that triggers these responses. Overall, the collaboration between these three scientists led to significant advancements in the understanding of exercise physiology. [Extracted from the article]

The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control, serving as a significant source of synaptic input to the spinal cord. Experimental studies have shown that gene expression in individual VLM neurons is predictive of their function. However, the molecular and cellular organization of the VLM has remained uncertain. This study aimed to create a comprehensive dataset of VLM cells using single-cell RNA sequencing in male and female mice. The dataset was enriched with targeted sequencing of spinally-projecting and adrenergic/noradrenergic VLM neurons. Based on differentially expressed genes, the resulting dataset of 114,805 VLM cells identifies 23 subtypes of neurons, excluding those in the inferior olive, and five subtypes of astrocytes. Spinally-projecting neurons were found to be abundant in seven subtypes of neurons, which were validated through in situ hybridization. These subtypes included adrenergic/noradrenergic neurons, serotonergic neurons, and neurons expressing gene markers associated with premotor neurons in the ventromedial medulla. Further analysis of adrenergic/noradrenergic neurons and serotonergic neurons identified nine and six subtypes, respectively, within each class of monoaminergic neurons. Marker genes that identify the neural network responsible for breathing were concentrated in two subtypes of neurons, delineated from each other by markers for excitatory and inhibitory neurons. These datasets are available for public download and for analysis with a user-friendly interface. Collectively, this study provides a fine-scale molecular identification of cells in the VLM, forming the foundation for a better understanding of the VLM's role in vital functions and motor control. [ABSTRACT FROM AUTHOR]

Rationale: Recent efforts in bioengineering and embryonic stem cell (ESC) technology allowed the generation of ESC-derived mouse lung tissues in transgenic mice that were missing critical morphogenetic genes. Epithelial cell lineages were efficiently generated from ESC, but other cell types were mosaic. A complete contribution of donor ESCs to lung tissue has never been achieved. The mouse lung has never been generated in a rat. Objective: We sought to generate the mouse lung in a rat. Methods: Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome editing was used to disrupt the Nkx2-1 gene in rat one-cell zygotes. Interspecies mouse–rat chimeras were produced by injection of wild-type mouse ESCs into Nkx2-1–deficient rat embryos with lung agenesis. The contribution of mouse ESCs to the lung tissue was examined by immunostaining, flow cytometry, and single-cell RNA sequencing. Measurements and Main Results: Peripheral pulmonary and thyroid tissues were absent in rat embryos after CRISPR-Cas9–mediated disruption of the Nkx2-1 gene. Complementation of rat Nkx2-1−/− blastocysts with mouse ESCs restored pulmonary and thyroid structures in mouse–rat chimeras, leading to a near-99% contribution of ESCs to all respiratory cell lineages. Epithelial, endothelial, hematopoietic, and stromal cells in ESC-derived lungs were highly differentiated and exhibited lineage-specific gene signatures similar to those of respiratory cells from the normal mouse lung. Analysis of receptor–ligand interactions revealed normal signaling networks between mouse ESC-derived respiratory cells differentiated in a rat. Conclusions: A combination of CRISPR-Cas9 genome editing and blastocyst complementation was used to produce mouse lungs in rats, making an important step toward future generations of human lungs using large animals as "bioreactors." [ABSTRACT FROM AUTHOR]

The nucleus tractus solitarii (NTS) plays a critical role in the homeostatic regulation of respiration, blood pressure, sodium consumption and metabolic processes. Despite their significance, the circuitry mechanisms facilitating these diverse physiological functions remain incompletely understood. In this study, we present a whole-brain mapping of both the afferent and efferent connections of Phox2b-expressing and GABAergic neurons within the NTS. Our findings reveal that these neuronal populations not only receive monosynaptic inputs primarily from the medulla oblongata, pons, midbrain, supra-midbrain and cortical areas, but also mutually project their axons to these same locales. Moreover, intense monosynaptic inputs are received from the central amygdala, the paraventricular nucleus of the hypothalamus, the parasubthalamic nucleus and the intermediate reticular nucleus, along with brainstem nuclei explicitly engaged in respiratory regulation. In contrast, both neuronal groups extensively innervate brainstem nuclei associated with respiratory functions, although their projections to regions above the midbrain are comparatively limited. These anatomical findings provide a foundational platform for delineating an anatomical framework essential for dissecting the specific functional mechanisms of these circuits. [ABSTRACT FROM AUTHOR]

Denitrification, a crucial biochemical pathway prevalent among haloarchaea in hypersaline ecosystems, has garnered considerable attention in recent years due to its ecological implications. Nevertheless, the underlying molecular mechanisms and genetic regulation governing this respiration/detoxification process in haloarchaea remain largely unexplored. In this study, RNA-sequencing was used to compare the transcriptomes of the haloarchaeon Haloferax mediterranei under oxic and denitrifying conditions, shedding light on the intricate metabolic alterations occurring within the cell, such as the accurate control of the metal homeostasis. Furthermore, the investigation identifies several genes encoding transcriptional regulators and potential accessory proteins with putative roles in denitrification. Among these are bacterioopsin-like transcriptional activators, proteins harboring a domain of unknown function (DUF2249), and cyanoglobin. In addition, the study delves into the genetic regulation of denitrification, finding a regulatory motif within promoter regions that activates numerous denitrification-related genes. This research serves as a starting point for future molecular biology studies in haloarchaea, offering a promising avenue to unravel the intricate mechanisms governing haloarchaeal denitrification, a pathway of paramount ecological importance. [ABSTRACT FROM AUTHOR]

Recordings from pre-Bötzinger complex neurons responsible for the inspiratory phase of the respiratory rhythm reveal a ramping burst pattern, starting around the time that the transition from expiration to inspiration begins, in which the spike rate gradually rises until a transition into a high-frequency burst occurs. The spike rate increase along the burst is accompanied by a gradual depolarization of the plateau potential that underlies the spikes. These effects may be functionally important for inducing the onset of inspiration and hence maintaining effective respiration; however, most mathematical models for inspiratory bursting do not capture this activity pattern. Here, we study how the modulation of spike height and afterhyperpolarization via the slow inactivation of an inward current can support various activity patterns including ramping bursts. We use dynamical systems methods designed for multiple timescale systems, such as bifurcation analysis based on timescale decomposition and averaging over fast oscillations, to generate an understanding of and predictions about the specific dynamic effects that lead to ramping bursts. We also analyze how transitions between ramping and other activity patterns may occur with parameter changes, which could be associated with experimental manipulations, environmental conditions, and/or development. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa) faces challenges to yield and quality due to urbanisation, deforestation and climate change, which has exacerbated high night temperature (HNT). This review explores the impacts of HNT on the physiological, molecular and agronomic aspects of rice growth. Rise in minimum temperature threatens a potential 41% reduction in rice yield by 2100. HNT disrupts rice growth stages, causing reduced seed germination, biomass, spikelet sterility and poor grain development. Recent findings indicate a 4.4% yield decline for every 1°C increase beyond 27°C, with japonica ecotypes exhibiting higher sensitivity than indica. We examine the relationships between elevated CO2, nitrogen regimes and HNT, showing that the complexity of balancing positive CO2 effects on biomass with HNT challenges. Nitrogen enrichment proves crucial during the vegetative stage but causes disruption to reproductive stages, affecting grain yield and starch synthesis. Additionally, we elucidate the impact of HNT on plant respiration, emphasising mitochondrial respiration, photorespiration and antioxidant responses. Genomic techniques, including CRISPR-Cas9, offer potential for manipulating genes for HNT tolerance. Plant hormones and carbohydrate enzymatic activities are explored, revealing their intricate roles in spikelet fertility, grain size and starch metabolism under HNT. Gaps in understanding genetic factors influencing heat tolerance and potential trade-offs associated with hormone applications remain. The importance of interdisciplinary collaboration is needed to provide a holistic approach. Research priorities include the study of regulatory mechanisms, post-anthesis effects, cumulative HNT exposure and the interaction between climate variability and HNT impact to provide a research direction to enhance rice resilience in a changing climate. We explore the impact of high night temperature (HNT) on rice phenomics, physiology and grain yield. From accelerated vegetative growth to changes in reproductive phases and enzymatic activities, we review how HNT affects rice in elevated CO2 and nitrogen environments to provide insights into photosynthesis, respiration and hormonal regulation, and their effect on grain yield and quality. This article belongs to the Collection Functional Genomics for Developing Climate Resilient Crops. [ABSTRACT FROM AUTHOR]

Anuran skin preserves all functional activities, especially for respiration and water regulation. Duttaphrynus melanostictus and Fejervarya limnocharis are the common species found in Borneo lowlands and are well-adapted to humans. Hence, they can reproduce quickly and rapidly in great numbers in the urban area. This study aims to select these urban-type anurans and describe the skin structure and glands. Four regions of skin samples were obtained, namely Dorsal Head (DH), Dorsal Centre (DC), Ventral Head (VH) and Ventral Centre (VC). The microscopic slides were prepared accordingly as in the histological techniques including skin grossing, fixing, processing, embedding, sectioning and were stained with Haematoxylin and Eosin staining. The seromucous glands are most prevalent in all four regions for both species. Parotoid glands are clearly visible in the skin structure of D. melanostictus, while there is a lack of parotoid glands in F. limnocharis. Nonetheless, F. limnocharis contains regular rows of glands, whereas the distribution of glands in D. melanostictus is scattered. In addition, D. melanostictus possess dermal bones, which are absent in F. limnocharis. Since anuran skin is a mucosal surface that in constant direct contact with the environment, their adaptations to harsh habitats should be reflected in the skin, particularly in the urban and invasive species in this study. [ABSTRACT FROM AUTHOR]

Establishing the temperature dependence of respiration is critical for accurate predictions of the global carbon cycle under climate change. Diurnal temperature fluctuations, or changes in substrate availability, lead to variations in leaf respiration. Additionally, recent studies hint that the thermal sensitivity of respiration could be time‐dependent. However, the role for endogenous processes, independent from substrate availability, as drivers of temporal changes in the sensitivity of respiration to temperature across phylogenies has not yet been addressed. Here, we examined the diurnal variation in the response of respiration to temperatures (R–T relationship) for different lycophyte, fern, gymnosperm and angiosperm species. We tested whether time‐dependent changes in the R–T relationship would impact leaf level respiration modelling. We hypothesized that interactions between endogenous processes, like the circadian clock, and leaf respiration would be independent from changes in substrate availability. Overall, we observed a time‐dependent sensitivity in the R–T relationship across phylogenies, independent of temperature, that affected modelling parameters. These results are compatible with circadian gating of respiration, but further studies should analyse the possible involvement of the clock. Our results indicate time‐dependent regulation of respiration might be widespread across phylogenies, and that endogenous regulation of respiration is likely affecting leaf‐level respiration fluxes. Summary statement: We observed that the sensitivity of respiration to temperature varied temporally across phylogenies, independent of temperature. Our findings highlight that time‐dependent regulation of respiration might be widespread across lycophytes, ferns, gymnosperms and angiosperms. [ABSTRACT FROM AUTHOR]

Photosynthesis is responsible for sustained plant productivity and ensures food supply. The change in global climatic patterns affects photosynthesis that subsequently reduces plant yield and poses threat to food security. Photosynthesis relies on a dual nature enzyme ribulose 1, 5 bisphosphate carboxylase oxygenase (Rubisco), which can fix CO2 as well as O2. The fixation rate of CO2 to O2 depends upon the relative concentration of CO2 inside chloroplast. Higher level of CO2 results in improved photosynthesis, however, its concentration depends upon environmental conditions. Under adverse climate conditions, the CO2 level drops down that leads to increased oxygenation which impedes the photosynthesis and reduces plant productivity. The impact is more significant and apparent specifically in C3 plants. Attempts have been made to address the loss in photosynthesis and multiple strategies have been adapted to date that focus on improvement of photosynthesis in C3 plants. In this review, we have discussed the multiple strategies being employed by different researchers to date for improvement of photosynthesis. The strategies discussed in this review include: improving the performance of Rubisco, engineering CO2-concentrating mechanism of C4 photosynthesis into C3 species, transformation of bicarbonate transporters from cyanobacteria into chloroplasts of C3 plants, and establishment of photorespiratory bypasses to catabolise toxic glycolate in shortest possible pathway. [ABSTRACT FROM AUTHOR]

Breathing is a natural daily action that one cannot do without, and it sensitively and intensely changes under various situations. What if this essential act of breathing can impact our overall well-being? Recent studies have demonstrated that breathing oscillations couple with higher brain functions, i.e., perception, motor actions, and cognition. Moreover, the timing of breathing, a phase transition from exhalation to inhalation, modulates specific cortical activity and accuracy in cognitive tasks. To determine possible respiratory roles in attentional and memory processes and functional neural networks, we discussed how breathing interacts with the brain that are measured by electrophysiology and functional neuroimaging: (i) respiration-dependent modulation of mental health and cognition; (ii) respiratory rhythm generation and respiratory pontomedullary networks in the brainstem; (iii) respiration-dependent effects on specific brainstem regions and functional neural networks (e.g., glutamatergic PreBötzinger complex neurons, GABAergic parafacial neurons, adrenergic C1 neurons, parabrachial nucleus, locus coeruleus, temporoparietal junction, default-mode network, ventral attention network, and cingulo-opercular salience network); and (iv) a potential application of breathing manipulation in mental health care. These outlines and considerations of "brain–breath" interactions lead to a better understanding of the interoceptive and cognitive mechanisms that underlie brain–body interactions in health conditions and in stress-related and neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a chronic and complex disease, and traditional drugs have many side effects. The active compound dihydromyricetin (DHM), derived from natural plants, has been shown in our previous study to possess the potential for reducing blood glucose levels; however, its precise molecular mechanism remains unclear. In the present study, network pharmacology and transcriptomics were performed to screen the molecular targets and signaling pathways of DHM disturbed associated with T2DM, and the results were partially verified by molecular docking, RT-PCR, and Western blotting at in vivo levels. Firstly, the effect of DHM on blood glucose, lipid profile, and liver oxidative stress in db/db mice was explored and the results showed that DHM could reduce blood glucose and improve oxidative stress in the liver. Secondly, GO analysis based on network pharmacology and transcriptomics results showed that DHM mainly played a significant role in anti-inflammatory, antioxidant, and fatty acid metabolism in biological processes, on lipoprotein and respiratory chain on cell components, and on redox-related enzyme activity, iron ion binding, and glutathione transferase on molecular functional processes. KEGG system analysis results showed that the PI3K-Akt signaling pathway, IL17 signaling pathway, HIF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and TNF signaling pathway were typical signaling pathways disturbed by DHM in T2DM. Thirdly, molecular docking results showed that VEGFA, SRC, HIF1A, ESR1, KDR, MMP9, PPARG, and MAPK14 are key target genes, five genes of which were verified by RT-PCR in a dose-dependent manner. Finally, Western blotting results revealed that DHM effectively upregulated the expression of AKT protein and downregulated the expression of MEK protein in the liver of db/db mice. Therefore, our study found that DHM played a therapeutic effect partially by activation of the PI3K/AKT/MAPK signaling pathway. This study establishes the foundation for DHM as a novel therapeutic agent for T2DM. Additionally, it presents a fresh approach to utilizing natural plant extracts for chemoprevention and treatment of T2DM. [ABSTRACT FROM AUTHOR]

Emerging low-emission production technologies make ethanol an interesting substrate for yeast biotechnology, but information on growth rates and biomass yields of yeasts on ethanol is scarce. Strains of 52 Saccharomycotina yeasts were screened for growth on ethanol. The 21 fastest strains, among which representatives of the Phaffomycetales order were overrepresented, showed specific growth rates in ethanol-grown shake-flask cultures between 0.12 and 0.46 h−1. Seven strains were studied in aerobic, ethanol-limited chemostats (dilution rate 0.10 h−1). Saccharomyces cerevisiae and Kluyveromyces lactis , whose genomes do not encode Complex-I-type NADH dehydrogenases, showed biomass yields of 0.59 and 0.56 gbiomass gethanol−1, respectively. Different biomass yields were observed among species whose genomes do harbour Complex-I-encoding genes: Phaffomyces thermotolerans (0.58 g g−1), Pichia ethanolica (0.59 g g−1), Saturnispora dispora (0.66 g g−1), Ogataea parapolymorpha (0.67 g g−1), and Cyberlindnera jadinii (0.73 g g−1). Cyberlindnera jadinii biomass showed the highest protein content (59 ± 2%) of these yeasts. Its biomass yield corresponded to 88% of the theoretical maximum that is reached when growth is limited by assimilation rather than by energy availability. This study suggests that energy coupling of mitochondrial respiration and its regulation will become key factors for selecting and improving yeast strains for ethanol-based processes. [ABSTRACT FROM AUTHOR]

Plants have evolved complicated defense and adaptive systems to grow in various abiotic stress environments such as drought, cold, and salinity. Anthocyanins belong to the secondary metabolites of flavonoids with strong antioxidant activity in response to various abiotic stress and enhance stress tolerance. Anthocyanin accumulation often accompanies the resistance to abiotic stress in plants to scavenge reactive oxygen species (ROS). Recent research evidence showed that many regulatory pathways such as osmoregulation, antioxidant response, plant hormone response, photosynthesis, and respiration regulation are involved in plant adaption to stress. However, the molecular regulatory mechanisms involved in controlling anthocyanin biosynthesis in relation to abiotic stress response have remained obscure. Here, we summarize the current research progress of specific regulators including small RNAs, and lncRNAs involved in the molecular regulation of abiotic stress-induced anthocyanin biosynthesis. In addition, an integrated regulatory network of anthocyanin biosynthesis controlled by microRNAs (miRNAs), long non-coding RNAs (lncRNAs), transcription factors, and stress response factors is also discussed. Understanding molecular mechanisms of anthocyanin biosynthesis for ROS scavenging in various abiotic stress responses will benefit us for resistance breeding in crop plants. [ABSTRACT FROM AUTHOR]

Hepatic sinusoidal obstruction syndrome (HSOS) is a death-dealing liver disease with a fatality rate of up to 67%. In the study present, we explored the efficacy of andrographolide (Andro), a diterpene lactone from Andrographis Herba, in ameliorating the monocrotaline (MCT)-induced HSOS and the underlying mechanism. The alleviation of Andro on MCT-induced rats HSOS was proved by biochemical index detection, electron microscope observation, and liver histological evaluation. Detection of hepatic ATP content, mitochondrial DNA (mtDNA) copy number, and protein expression of nuclear respiratory factor-1 (NRF1) and peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) demonstrated that Andro strengthened mitochondrial biogenesis in livers from MCT-treated rats. Chromatin immunoprecipitation assay exhibited that Andro enhanced the occupation of nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) in the promoter regions of both PPARGC1A and NRF1. Andro also activated the NRF2-dependent anti-oxidative response and alleviated liver oxidative injury. In Nrf2 knock-out mice, MCT induced more severe liver damage, and Andro showed no alleviation in it. Furthermore, the Andro-activated mitochondrial biogenesis and anti-oxidative response were reduced in Nrf2 knock-out mice. Contrastingly, knocking out Kelch-like ECH-associated protein 1 (Keap1), a NRF2 repressor, reduced MCT-induced liver damage. Results from co-immunoprecipitation, molecular docking analysis, biotin-Andro pull-down, cellular thermal shift assay, and surface plasmon resonance assay showed that Andro hindered the NRF2-KEAP1 interaction via directly binding to KEAP1. In conclusion, our results revealed that NRF2-dependent liver mitochondrial biogenesis and anti-oxidative response were essential for the Andro-provided alleviation of the MCT-induced HSOS. Graphical Headlights: 1. Andro alleviated MCT-induced HSOS via activating antioxidative response and promoting mitochondrial biogenesis. 2. Andro-activated antioxidative response and mitochondrial biogenesis were NRF2-dependent. 3. Andro activated NRF2 via binding to KEAP1. [ABSTRACT FROM AUTHOR]

Chronic hypercapnia (CH) is a hallmark of respiratory-related diseases, and the level of hypercapnia can acutely or progressively become more severe. Previously, we have shown time-dependent adaptations in steady-state physiology during mild (arterial PCO2 ~55 mmHg) and moderate (~60 mmHg) CH in adult goats, including transient (mild CH) or sustained (moderate CH) suppression of acute chemosensitivity suggesting limitations in adaptive respiratory control mechanisms as the level of CH increases. Changes in specific markers of glutamate receptor plasticity, interleukin-1ß, and serotonergic modulation within key nodes of cardiorespiratory control do not fully account for the physiological adaptations to CH. Here, we used an unbiased approach (bulk tissue RNA sequencing) to test the hypothesis that mild or moderate CH elicits distinct gene expression profiles in important brain stem regions of cardiorespiratory control, which may explain the contrasting responses to CH. Gene expression profiles from the brain regions validated the accuracy of tissue biopsy methodology. Differential gene expression analyses revealed greater effects of CH on brain stem sites compared with the medial prefrontal cortex. Mild CH elicited an upregulation of predominantly immune-related genes and predicted activation of immune-related pathways and functions. In contrast, moderate CH broadly led to downregulation of genes and predicted inactivation of cellular pathways related to the immune response and vascular function. These data suggest that mild CH leads to a steady-state activation of neuroinflammatory pathways within the brain stem, whereas moderate CH drives the opposite response. Transcriptional shifts in immune-related functions may underlie the cardiorespiratory network's capability to respond to acute, more severe hypercapnia when in a state of progressively increased CH. NEW & NOTEWORTHY Mild chronic hypercapnia (CH) broadly upregulated immune-related genes and a predicted activation of biological pathways related to immune cell activity and the overall immune response. In contrast, moderate CH primarily downregulated genes related to major histocompatibility complex signaling and vasculature function that led to a predicted inactivation of pathways involving the immune response and vascular endothelial function. The severity-dependent effect on immune responses suggests that neuroinflammation has an important role in CH and may be important in the maintenance of proper ventilatory responses to acute and chronic hypercapnia. [ABSTRACT FROM AUTHOR]

Tamoxifen is one of the most effective therapeutic tools for estrogen receptor-positive (ER +) breast cancer. However, the intrinsic insensitivity and resistance to tamoxifen remains a significant hurdle for achieving optimal responses and curative therapy. In this study, we report that F-box and leucine-rich repeat protein 16 (FBXL16) is located in the mitochondria of ER + breast cancer cells. The mitochondrial FBXL16 plays an essential role in sustaining mitochondrial respiration and thereby regulates the sensitivity of ER + breast cancer cells to tamoxifen treatment. Importantly, high FBXL16 expression is significantly correlated with poor overall survival of ER + breast cancer patients. Moreover, mitochondrial inhibition phenocopies FBXL16 depletion in terms of sensitizing the ER + breast cancer cells to tamoxifen treatment. Together, our study demonstrates that FBXL16 acts as a novel regulator of tamoxifen sensitivity. Thus, targeting FBXL16 may serve as a promising approach for improving the therapeutic efficacy of tamoxifen in ER + breast cancer cells. [ABSTRACT FROM AUTHOR]

Mitochondrial metabolism is entirely dependent on the biosynthesis of the [4Fe-4S] clusters, which are part of the subunits of the respiratory chain. The mitochondrial late ISC pathway mediates the formation of these clusters from simpler [2Fe-2S] molecules and transfers them to client proteins. Here, we characterized the late ISC pathway in one of the simplest mitochondria, mitosomes, of the anaerobic protist Giardia intestinalis that lost the respiratory chain and other hallmarks of mitochondria. In addition to IscA2, Nfu1 and Grx5 we identified a novel BolA1 homologue in G. intestinalis mitosomes. It specifically interacts with Grx5 and according to the high-affinity pulldown also with other core mitosomal components. Using CRISPR/Cas9 we were able to establish full bolA1 knock out, the first cell line lacking a mitosomal protein. Despite the ISC pathway being the only metabolic role of the mitosome no significant changes in the mitosome biology could be observed as neither the number of the mitosomes or their capability to form [2Fe-2S] clusters in vitro was affected. We failed to identify natural client proteins that would require the [2Fe-2S] or [4Fe-4S] cluster within the mitosomes, with the exception of [2Fe-2S] ferredoxin, which is itself part of the ISC pathway. The overall uptake of iron into the cellular proteins remained unchanged as also observed for the grx5 knock out cell line. The pull-downs of all late ISC components were used to build the interactome of the pathway showing specific position of IscA2 due to its interaction with the outer mitosomal membrane proteins. Finally, the comparative analysis across Metamonada species suggested that the adaptation of the late ISC pathway identified in G. intestinalis occurred early in the evolution this of supergroup of eukaryotes. Author summary: Anaerobic parasitic protists, such as Giardia intestinalis, have dramatically reduced their mitochondrial metabolism. Large mitochondrial networks known from aerobic eukaryotes have evolved into minimalist vesicles that are still enclosed by a double membrane but have lost the mitochondrial genome, respiratory chain, and most mitochondrial enzymes. However, these small mitochondria still contain the so-called ISC pathway, which synthesizes iron-sulfur clusters, essential cofactors for the function of respiratory chain complexes, and other mitochondrial enzymes. In this work, we have begun to characterize the ISC pathway in G. intestinalis to understand whether and why iron-sulfur clusters are formed in these small mitochondrial organelles known as mitosomes. We found that while the 'early' part of the ISC pathway responsible for the formation of the simplest [2Fe-2S] clusters is functional in mitosomes, the function of the 'late' components involved in [4Fe-4S] cluster formation remains unclear due to unknown substrates that require these clusters. Identifying the role of the "late" ISC pathway is crucial to understanding why mitosomes remain present in anaerobic eukaryotes at all. [ABSTRACT FROM AUTHOR]

In the treatment of bronchial asthma (BA), an integrated approach is used that includes both drugs and alternative methods that influence the psycho-emotional state of the patient. In this regard, one of the most powerful methods of psycho-emotional influence on a person is musical influence. The aim of the research is to study the effectiveness of influence of audio signals of different amplitude-frequency range on the central mechanisms of regulation of ventilatory capacity of bronchi of patients with asthma. Material and methods. Twenty-five children between the ages of 9 and 14 with clinically diagnosed BA participated in the study. Three melodies with different component composition were used. Their amplitude-frequency characteristics were analyzed using the Matlab environment. The sound energy fraction of the studied musical compositions in one-third octave frequency bands throughout the duration of the audio signal was calculated. Statistical processing of the data was performed using IBM SPSS Statistics software. Results. The results of the study indicate that the most effective musical influence is provided by the audio excerpt from The Magic Flute by W. A. Mozart. It was found that the main spirographic indicators of bronchopulmonary obstruction increase under the influence of music, and correspondingly there are changes in the integral characteristics of bioelectrical activity of the brain. Conclusion. The results of the study show reliable normalization of spirography indicators in children with bronchial asthma under the influence of selected musical melodies of a certain frequency. Effectiveness of sound influence on central regulation mechanisms of bronchial ventilatory capacity can be used for preventive and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic--clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic--clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed. [ABSTRACT FROM AUTHOR]

Purpose: Although cisplatin-containing chemotherapy has been utilized as a front-line treatment for cervical cancer, intrinsic and acquired resistance of cisplatin remains a major hurdle for the durable and curative therapeutic response. We thus aim to identify novel regulator of cisplatin resistance in cervical cancer cells. Methods: Real-time PCR and western blotting analysis were employed to determine the expression of BRSK1 in normal and cisplatin-resistant cells. Sulforhodamine B assay was conducted to assess the sensitivity of cervical cancer cells to cisplatin. Seahorse Cell Mito Stress Test assay was utilized to evaluate the mitochondrial respiration in cervical cancer cells. Results: BRSK1 expression was upregulated in cisplatin-treated cervical cancer patient tumors and cell lines compared with untreated tumors and cell lines. Depletion of BRSK1 significantly enhanced the sensitivity of both normal and cisplatin-resistant cervical cancer cells to cisplatin treatment. Moreover, BRSK1-mediated regulation of cisplatin sensitivity is conducted by a subpopulation of BRSK1 residing in the mitochondria of cervical cancer cells and is dependent on its kinase enzymatic activity. Mechanistically, BRSK1 confers cisplatin resistance via the regulation of mitochondrial respiration. Importantly, treatment with mitochondrial inhibitor in cervical cancer cells phenocopied the BRSK1 depletion-mediated mitochondria dysfunction and cisplatin sensitization. Of note, we observed that high BRSK1 expression is correlated with poor prognosis in cisplatin-treated cervical cancer patients. Conclusion: Our study defines BRSK1 as a novel regulator of cisplatin sensitivity, identifying that targeting BRSK1-regulated mitochondrial respiration could be a useful approach for enhancing the efficacy of cisplatin-based chemotherapy in cervical cancer patients. [ABSTRACT FROM AUTHOR]

Heterotrophic bacteria play a vital role in the marine carbon cycle and viruses are an important regulator of bacterial metabolism and community composition. It remains unclear about how bacteria‐virus interactions vary with environmental conditions in oceans. In this study, bacterial metabolic activity and community composition were examined in three treatments with different viral pressure (control, virus‐rich and virus‐reduced) through bioassay experiments at three stations with different environmental conditions in the shelf of the northern South China Sea. Our results showed that bacteria‐virus interactions varied with environmental conditions. Viral lysis mediated bacterial growth rate (BGR) and production by shaping bacterial community composition. Furthermore, the effect of viral lysis on bacterial growth rate and production was reduced in substrate‐rich waters compared to substrate‐low waters. However, the opposite pattern occurred for viral regulation on bacterial respiration and carbon demand, likely since viral lysis dramatically mitigated the maintenance respiration of bacteria. Consequently, viral lysis to greater extent mitigated bacterial carbon processing in substrate‐rich environments than in substrate‐low environments. Our findings provided new insights into bacteria‐virus interactions, and improved our understanding of the role microbial processes in carbon cycling in oceans. Plain Language Summary: Heterotrophic bacteria play important roles in marine biogeochemical cycle and their viruses manipulate these processes. We found that viral regulation of bacterial metabolism varied with environmental conditions and the two aspects of bacterial metabolism responded differently to viral lysis. The reductions of bacterial growth rate and production caused by viral lysis increased from nearshore to offshore seawaters, while viral regulations on bacterial respiration and carbon demand showed the opposite pattern. The reasons for differences in the regulation of bacterial metabolism by virus varied with environmental conditions may be that high substrate supply in nearshore waters improved antiviral defense and dramatically mitigated the maintenance respiration of bacteria. In general, viral lysis to greater extent mitigated bacterial carbon processing in substrate‐rich environments than in substrate‐low environments. Our study provided new insights into the interactions of bacterial metabolism with viruses, and improved our understanding of marine carbon cycle in contrasting trophic environments. Key Points: Viral lysis reduced bacterial growth rate and production less in the substrate‐rich waters than oligotrophic watersVirus‐induced losses in bacterial respiration and carbon demand decreased offshoreViral lysis mitigated bacterial carbon processing more in substrate‐rich environments than in oligotrophic environments [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S), the third gasotransmitter, has positive roles in animals and plants. Mitochondria are the source and the target of H2S and the regulatory hub in metabolism, stress, and disease. Mitochondrial bioenergetics is a vital process that produces ATP and provides energy to support the physiological and biochemical processes. H2S regulates mitochondrial bioenergetic functions and mitochondrial oxidative phosphorylation. The article summarizes the recent knowledge of the chemical and biological characteristics, the mitochondrial biosynthesis of H2S, and the regulatory effects of H2S on the tricarboxylic acid cycle and the mitochondrial respiratory chain complexes. The roles of H2S on the tricarboxylic acid cycle and mitochondrial respiratory complexes in mammals have been widely studied. The biological function of H2S is now a hot topic in plants. Mitochondria are also vital organelles regulating plant processes. The regulation of H2S in plant mitochondrial functions is gaining more and more attention. This paper mainly summarizes the current knowledge on the regulatory effects of H2S on the tricarboxylic acid cycle (TCA) and the mitochondrial respiratory chain. A study of the roles of H2S in mitochondrial respiration in plants to elucidate the botanical function of H2S in plants would be highly desirable. [ABSTRACT FROM AUTHOR]

The Mulibrey (Muscle–liver–brain–eye) nanism caused by loss-of-function variants in TRIM37 gene is an autosomal recessive disorder characterized by severe growth failure and constrictive pericarditis. These patients also suffer from severe respiratory infections, co-incident with an increased mortality rate. Here, we revealed that TRIM37 variants were associated with recurrent infection. Trim37 FINmajor (a representative variant of Mulibrey nanism patients) and Trim37 knockout mice were susceptible to influenza virus infection. These mice showed defects in follicular helper T (TFH) cell development and antibody production. The effects of Trim37 on TFH cell differentiation relied on its E3 ligase activity catalyzing the K27/29-linked polyubiquitination of Bcl6 and its MATH domain-mediated interactions with Bcl6, thereby protecting Bcl6 from proteasome-mediated degradation. Collectively, these findings highlight the importance of the Trim37-Bcl6 axis in controlling the development of TFH cells and the production of high-affinity antibodies, and further unveil the immunologic mechanism underlying recurrent respiratory infection in Mulibrey nanism. [ABSTRACT FROM AUTHOR]

Opioids depress breathing by inhibition of interconnected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a population of neurons in the dorsolateral pons, particularly the Kölliker-Fuse (KF) nucleus, that are key mediators of opioid-induced respiratory depression. However, the projection target and synaptic connections of MOR-expressing KF neurons are unknown. Here, we used retrograde labeling and brain slice electrophysiology to determine that MOR-expressing KF neurons project to respiratory nuclei in the ventrolateral medulla, including the preBötzinger complex (preBötC) and rostral ventral respiratory group (rVRG). These medullary-projecting, MOR-expressing dorsolateral pontine neurons express FoxP2 and are distinct from calcitonin gene-related peptide-expressing lateral parabrachial neurons. Furthermore, dorsolateral pontine neurons release glutamate onto excitatory preBötC and rVRG neurons via monosynaptic projections, which is inhibited by presynaptic opioid receptors. Surprisingly, the majority of excitatory preBötC and rVRG neurons receiving MOR-sensitive glutamatergic synaptic input from the dorsolateral pons are themselves hyperpolarized by opioids, suggesting a selective opioid-sensitive circuit from the KF to the ventrolateral medulla. Opioids inhibit this excitatory pontomedullary respiratory circuit by three distinct mechanisms--somatodendritic MORs on dorsolateral pontine and ventrolateral medullary neurons and presynaptic MORs on dorsolateral pontine neuron terminals in the ventrolateral medulla--all of which could contribute to opioid-induced respiratory depression. [ABSTRACT FROM AUTHOR]

Respiration-rhythmic oscillations in the local field potential emerge in the mPFC, a cortical region with a key role in the regulation of cognitive and emotional behavior. Respiration-driven rhythms coordinate local activity by entraining fast c oscillations as well as single-unit discharges. To what extent respiration entrainment differently engages the mPFC network in a behavioral state-dependent manner, however, is not known. Here, we compared the respiration entrainment of mouse PFC local field potential and spiking activity (23 male and 2 female mice) across distinct behavioral states: during awake immobility in the home cage (HC), during passive coping in response to inescapable stress under tail suspension (TS), and during reward consumption (Rew). Respiration-driven rhythms emerged during all three states. However, prefrontal c oscillations were more strongly entrained by respiration during HC than TS or Rew. Moreover, neuronal spikes of putative pyramidal cells and putative interneurons showed significant respiration phase-coupling throughout behaviors with characteristic phase preferences depending on the behavioral state. Finally, while phase-coupling dominated in deep layers in HC and Rew conditions, TS resulted in the recruitment of superficial layer neurons to respiration. These results jointly suggest that respiration dynamically entrains prefrontal neuronal activity depending on the behavioral state. [ABSTRACT FROM AUTHOR]

Copyright of Environmental Science & Technology (10036504) is the property of Editorial Board of Environmental Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Sleep disorder is often the first symptom of age-related cognitive decline associated with Alzheimer's disease (AD) observed in primary care. The relationship between sleep and early AD was examined using a patented sleep mattress designed to record respiration and high frequency movement arousals. A machine learning algorithm was developed to classify sleep features associated with early AD. Method: Community-dwelling older adults (N = 95; 62–90 years) were recruited in a 3-h catchment area. Study participants were tested on the mattress device in the home bed for 2 days, wore a wrist actigraph for 7 days, and provided sleep diary and sleep disorder self-reports during the 1-week study period. Neurocognitive testing was completed in the home within 30-days of the sleep study. Participant performance on executive and memory tasks, health history and demographics were reviewed by a geriatric clinical team yielding Normal Cognition (n = 45) and amnestic MCI-Consensus (n = 33) groups. A diagnosed MCI group (n = 17) was recruited from a hospital memory clinic following diagnostic series of neuroimaging biomarker assessment and cognitive criteria for AD. Results: In cohort analyses, sleep fragmentation and wake after sleep onset duration predicted poorer executive function, particularly memory performance. Group analyses showed increased sleep fragmentation and total sleep time in the diagnosed MCI group compared to the Normal Cognition group. Machine learning algorithm showed that the time latency between movement arousals and coupled respiratory upregulation could be used as a classifier of diagnosed MCI vs. Normal Cognition cases. ROC diagnostics identified MCI with 87% sensitivity; 89% specificity; and 88% positive predictive value. Discussion: AD sleep phenotype was detected with a novel sleep biometric, time latency, associated with the tight gap between sleep movements and respiratory coupling, which is proposed as a corollary of sleep quality/loss that affects the autonomic regulation of respiration during sleep. Diagnosed MCI was associated with sleep fragmentation and arousal intrusion. [ABSTRACT FROM AUTHOR]

Abiotic stresses are various environmental factors that inhibit a normal plant growth and limit the crop productivity. Plant scientists have been attempting for a long time to understand how plants respond to these stresses and find an effective and feasible solution in mitigating their adverse impacts. Exogenous calcium ion as an essential element for the plant growth, development and reproduction has proven to be effective in alleviating plant stresses through enhancing its resistance or tolerance against them. With a comprehensive review of most recent advances and the analysis by VOSviewer in the researches on this focus of "exogenous calcium" and "stress" for last decade, this paper summarizes the mechanisms of exogenous calcium that are involved in plant defensive responses to abiotic stresses and classifies them accordingly into six categories: I) stabilization of cell walls and membranes; II) regulation of Na+ and K+ ratios; III) regulation of hormone levels in plants; IV) maintenance of photosynthesis; V) regulation of plant respiratory metabolism and improvement of root activities; and VI) induction of gene expressions and protein transcriptions for the stress resistance. Also, the progress and advances from the updated researches on exogenous calcium to alleviate seven abiotic stresses such as drought, flooding, salinity, high temperature, low temperature, heavy metals, and acid rain are outlined. Finally, the future research perspectives in agricultural production are discussed. [ABSTRACT FROM AUTHOR]

• SSRIs and 5-HT 2 agonists had differential effects on postictal breathing in kindled mice. • Different 5-HT receptor pathways modulate postictal breathing on distinct timescales. • Treatments were less effective at promoting breathing when seizures occurred during sleep. • Citalopram and fluoxetine pretreatment eliminated ictal and postictal apnea. Seizures can cause profound breathing disruptions. Seizures arising from sleep cause greater breathing impairment than those emerging from wakefulness and more often result in sudden unexpected death in epilepsy (SUDEP). The neurotransmitter serotonin (5-HT) plays a major role in respiration and sleep-wake regulation. 5-HT modulates seizure susceptibility and severity and is dysregulated by seizures. Thus, the impact of seizures on breathing dysregulation may be due to impaired 5-HT neurotransmission. We examined whether pharmacologically increasing 5-HT neurotransmission prior to seizures improves postictal breathing and how sleep-state during seizure induction contributes to these effects. We assessed breathing with whole-body plethysmography in 84 amygdala-kindled mice pre-treated with selective serotonin reuptake inhibitors (SSRI) or 5-HT 2 receptor agonists. SSRIs and 5-HT 2 agonists increased postictal breathing frequency (f R), tidal volume (V T), and minute ventilation (V E) at different timepoints following seizures induced during wakefulness. These effects were not observed following seizures induced during NREM sleep. SSRIs suppressed ictal and postictal apnea regardless of sleep state. The SSRI citalopram and the 5-HT 2 agonists TCB-2 and MK-212 decreased breathing variability following wake-occurring seizures at different postictal timepoints. Only MK-212 decreased breathing variability when seizures were induced during NREM sleep. The 5-HT 2A antagonist MDL-11939 reduced the effect of citalopram on f R , V T , and V E , and enhanced its effect on breathing variability in the initial period following a seizure. These results suggest that 5-HT mechanisms that are dependent on or independent from the 5-HT 2 family of receptors impact breathing on different timescales during the recovery of eupnea, and that certain serotonergic treatments may be less effective at facilitating postictal breathing following seizures emerging from sleep. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Chinese Institute of Food Science & Technology / Zhongguo Shipin Xuebao is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Doxorubicin (Dox), an anthracycline antibiotic, is an anticancer drug that inhibits DNA replication and cellular metabolic processes in cancer cells with high proliferative potential. However, Dox causes severe side effects, including myocardial damage and heart failure, but the molecular mechanism underlying Dox-induced myocardial injury remains uncertain. In the present study, we evaluated the effects of Dox on the mitochondrial quality control system and regulation of mitochondrial respiration and autophagy in an in vitro rat myoblast H9c2 cell culture model using western blotting, immunohistochemistry, the Seahorse XF24 system, and flow cytometry. Our results showed that Dox did not impair the initiation of autophagic flux or the functions of lysosomes; however, Dox affected the mitochondrial quality control system, leading to a fission-dominant morphology and impaired regulation of mitochondrial respiration, thereby increasing oxidative stress and inhibited progression of autophagy, particularly the fusion of autophagosomes with lysosomes. This inhibition caused a significant decrease in the formation of autolysosomes and was responsible for the accumulation of dysfunctional mitochondria and subsequent increase in oxidative stress, eventually leading to increased myocardial cell death. [Display omitted] • Doxorubicin impaired the regulation of mitochondrial respiration. • Doxorubicin increased mitochondrial reactive oxygen species production. • Doxorubicin inhibited the progression of autophagy, which increased cell death. • Doxorubicin inhibited interaction of the SNARE molecules SNAP29, STX17, and VAMP8. [ABSTRACT FROM AUTHOR]

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction. [ABSTRACT FROM AUTHOR]

The thermal compensatory response of microbial respiration contributes to a decrease in warming‐induced enhancement of soil respiration over time, which could weaken the positive feedback between the carbon cycle and climate warming. Climate warming is also predicted to cause a worldwide decrease in soil moisture, which has an effect on the microbial metabolism of soil carbon. However, whether and how changes in moisture affect the thermal compensatory response of microbial respiration are unexplored. Here, using soils from an 8‐year warming experiment in an alpine grassland, we assayed the thermal response of microbial respiration rates at different soil moisture levels. The results showed that relatively low soil moisture suppressed the thermal compensatory response of microbial respiration, leading to an enhanced response to warming. A subsequent moisture incubation experiment involving off‐plot soils also showed that the response of microbial respiration to 100 d warming shifted from a slight compensatory response to an enhanced response with decreasing incubation moisture. Further analysis revealed that such respiration regulation by moisture was associated with shifts in enzymatic activities and carbon use efficiency. Our findings suggest that future drought induced by climate warming might weaken the thermal compensatory capacity of microbial respiration, with important consequences for carbon–climate feedback. [ABSTRACT FROM AUTHOR]

Coenzyme Q (CoQ, aka ubiquinone) is a key component of the mitochondrial electron transport chain (ETC) and membrane-incorporated antioxidant. CoQ10 deficiencies encompass a heterogeneous spectrum of clinical phenotypes and can be caused by hereditary mutations in the biosynthesis pathway or result from pharmacological interventions such as HMG-CoA Reductase inhibitors, and statins, which are widely used to treat hypercholesterolemia and prevent cardiovascular disease. How CoQ deficiency affects individual tissues and cell types, particularly mitochondrial-rich ones such as brown adipose tissue (BAT), has remained poorly understood. Here we show that pharmacological and genetic models of BAT CoQ deficiency show altered respiration that can only in part be explained by classical roles of CoQ in the respiration chain. Instead, we found that CoQ strongly impacts brown and beige adipocyte respiration via the regulation of uncoupling protein 1 (UCP1) expression. CoQ deficiency in BAT robustly decreases UCP1 protein levels and uncoupled respiration unexpectedly, resulting in increased inner mitochondrial membrane potential and decreased ADP/ATP ratios. Suppressed UCP1 expression was also observed in a BAT-specific in vivo model of CoQ deficiency and resulted in enhanced cold sensitivity. These findings demonstrate an as yet unappreciated role of CoQ in the transcriptional regulation of key thermogenic genes and functions. [ABSTRACT FROM AUTHOR]

This article, titled "Reflections on alma mater: Origin and evolution of Ruhr University Bochum," discusses the establishment and development of Ruhr University Bochum in Germany. The university was founded in 1961 and officially opened in 1970. The article highlights the role of the university's founding fathers, including HH Loeschke and Johann Schwarzkopff, in planning and implementing a special research program known as "Sonderforschungsbereich" (SFB). The SFB focused on various areas of research, including biological signals, chemical signals, and the control of breathing and circulation. The article also mentions the challenges faced by the university during economic crises and emphasizes the importance of investing in research and education for the future. [Extracted from the article]

The article features an interview with Ana Julia Fernández-Alvarez and María Gabriela Thomas, the co-first authors of a paper titled "Smaug1 membrane-less organelles respond to AMPK and mTOR and affect mitochondrial function." The researchers discuss their findings on the protein Smaug1 and its role in regulating mitochondrial respiration. They explain that Smaug1 forms membrane-less organelles called biocondensates, which play a crucial role in coordinating the biogenesis of the respiratory machinery. The disruption of Smaug1 organelles has significant effects on mitochondrial morphology and function. The researchers express their admiration for the Journal of Cell Science and their excitement to continue their work in expanding their findings to different physiological systems. [Extracted from the article]

The ability to discriminate competing external stimuli and initiate contextually appropriate behaviours is a key brain function. Neurons in the deep superior colliculus (dSC) integrate multisensory inputs and activate descending projections to premotor pathways responsible for orienting, attention and defence, behaviours which involve adjustments to respiratory and cardiovascular parameters. However, the neural pathways that subserve the physiological components of orienting are poorly understood. We report that orienting responses to optogenetic dSC stimulation are accompanied by short‐latency autonomic, respiratory and electroencephalographic effects in awake rats, closely mimicking those evoked by naturalistic alerting stimuli. Physiological responses were not accompanied by detectable aversion or fear, and persisted under urethane anaesthesia, indicating independence from emotional stress. Anterograde and trans‐synaptic viral tracing identified a monosynaptic pathway that links the dSC to spinally projecting neurons in the medullary gigantocellular reticular nucleus (GiA), a key hub for the coordination of orienting and locomotor behaviours. In urethane‐anaesthetized animals, sympathoexcitatory and cardiovascular, but not respiratory, responses to dSC stimulation were replicated by optogenetic stimulation of the dSC–GiA terminals, suggesting a likely role for this pathway in mediating the autonomic components of dSC‐mediated responses. Similarly, extracellular recordings from putative GiA sympathetic premotor neurons confirmed short‐latency excitatory inputs from the dSC. This pathway represents a likely substrate for autonomic components of orienting responses that are mediated by dSC neurons and suggests a mechanism through which physiological and motor components of orienting behaviours may be integrated without the involvement of higher centres that mediate affective components of defensive responses. Key points: Neurons in the deep superior colliculus (dSC) integrate multimodal sensory signals to elicit context‐dependent innate behaviours that are accompanied by stereotypical cardiovascular and respiratory activities.The pathways responsible for mediating the physiological components of colliculus‐mediated orienting behaviours are unknown. We show that optogenetic dSC stimulation evokes transient orienting, respiratory and autonomic effects in awake rats which persist under urethane anaesthesia.Anterograde tracing from the dSC identified projections to spinally projecting neurons in the medullary gigantocellular reticular nucleus (GiA). Stimulation of this pathway recapitulated autonomic effects evoked by stimulation of dSC neurons.Electrophysiological recordings from putative GiA sympathetic premotor neurons confirmed short latency excitatory input from dSC neurons.This disynaptic dSC–GiA–spinal sympathoexcitatory pathway may underlie autonomic adjustments to salient environmental cues independent of input from higher centres. [ABSTRACT FROM AUTHOR]

The mechanism of death in Sudden infant death syndrome (SIDS) remains unknown but it is hypothesised that cardiorespiratory failure of brainstem origin results in early post-natal death. For a subset of SIDS infants, an underlying genetic cause may be present, and genetic abnormalities affecting brainstem respiratory control may result in abnormalities that are detectable before death. Genetic knockout mice models were developed in the 1990s and have since helped to elucidate the physiological roles of a number of genes. This systematic review aimed to identify which genes, when knocked out, result in the phenotypes of abnormal cardiorespiratory control and/or early post-natal death. Three major genes were identified: Pet1- a serotonin transcription factor, the neurotrophin pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor (PAC1). Knockouts targeting these genes had blunted hypercapnic and/or hypoxic responses and early post-natal death. The hypothesis that these genes have a role in SIDS is supported by their being identified as abnormal in SIDS cohorts. Future research in SIDS cohorts will be important to determine whether these genetic abnormalities coexist and their potential applicability as biomarkers. [ABSTRACT FROM AUTHOR]

The parabrachial nucleus (PBN) is a major hub that receives sensory information from both internal and external environments. Specific populations of PBN neurons are involved in behaviors including food and water intake, nociceptive responses, breathing regulation, as well as learning and responding appropriately to threatening stimuli. However, it is unclear how many PBN neuron populations exist and how different behaviors may be encoded by unique signaling molecules or receptors. Here we provide a repository of data on the molecular identity, spatial location, and projection patterns of dozens of PBN neuron subclusters. Using single-cell RNA sequencing, we identified 21 subclusters of neurons in the PBN and neighboring regions. Multiplexed in situ hybridization showed many of these subclusters are enriched within specific PBN subregions with scattered cells in several other regions. We also provide detailed visualization of the axonal projections from 21 Cre-driver lines of mice. These results are all publicly available for download and provide a foundation for further interrogation of PBN functions and connections. [ABSTRACT FROM AUTHOR]

The review addresses modern methods of electrical stimulation used to regulate the function of external respiration in humans. The methods include abdominal functional stimulation of respiratory muscles, diaphragmatic stimulation, phrenic nerve stimulation, epidural and transcutaneous spinal cord stimulation. The physiological rationale of their application is described along with the examples of their use in clinical practice, including stimulation parameters and electrode placement diagrams for each of the methods. We analyze the effectiveness of each of the methods in patients with respiratory muscle paresis and the features of their use depending on the level of spinal cord injury. Special attention is paid to the method of epidural spinal cord stimulation because this technique is widely used in electrophysiological studies on animal models, providing deeper insight into the spinal levels of the functional control of external respiration. The review substantiates the great potential of using the method of transcutaneous electrical spinal cord stimulation both in fundamental studies of external respiration and in clinical practice. [ABSTRACT FROM AUTHOR]

• 6-OHDA Parkinson's disease (PD) animal model causes significant respiratory deficits. • Apocynin prevents oxidative stress (OS) in respiratory nuclei in the 6-OHDA model. • Apocynin-mediated OS inhibition reduces respiratory neurodegeneration in the 6-OHDA model. • Apocynin inhibits OS, which prevents breathing impairment in the 6-OHDA PD model. • A new perspective to improve breathing and the quality of life of PD patients is provided. Parkinson's Disease (PD) is a neurogenerative disorder characterized by the death of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), leading to motor, cognitive, learning, and respiratory dysfunctions. New evidence revealed that breathing impairment in PD mainly results from oxidative stress (OS) that initiates apoptotic signaling in respiratory neurons. Here, we investigated the role of OS inhibition using apocynin (non-specific NADPH oxidase inhibitor) in a 6-OHDA PD animal model in the neural control of breathing. The PD model was confirmed with a 70% reduction in TH-expressing neurons within the SNpc. After 20 and 40 days of PD induction, no differences were observed in superoxide anion levels in any respiratory nuclei. At 30 days after PD induction, 6-OHDA animals presented OS that was prevented in all respiratory nuclei by adding apocynin to the drinking water for 10 days. Forty days after PD animal model induction, impaired motor and breathing function, reduced Phox2b and NK1 receptors-expressing neurons in the medullary respiratory areas; decreased latency to fall in the rotarod motor test; and attenuated respiratory frequency and minute ventilation parameters at rest and under hypercapnia conditions were observed. After 20 days of apocynin treatment, neurodegeneration of respiratory nuclei and breathing dysfunction in 6-OHDA animals were prevented. Thus, OS contributes to respiratory neuron death, consequently leading to breathing dysfunction in the 6-OHDA PD animal model. Furthermore, these results present a new perspective for preventing the onset and progression of PD-related respiratory impairments. [ABSTRACT FROM AUTHOR]

Radionuclide contamination has become a global environmental concern due to the high mobility and toxicity of certain isotopes. Bioreduction mediated by electrochemically active bacteria (EAB) with unique extracellular electron transfer (EET) capability is recognized as a promising approach for nuclear waste treatment. However, it is difficult to achieve bidirectional regulation of EET pathway through traditional genetic manipulation, limiting the bioremediation application of EAB. Here, we designed and optimized a novel Esa quorum sensing (EQS) system for highly efficient gene expression and interleaved cellular functional output. By promoting dimethyl sulfoxide reductase at low cell density and increasing the synthesis of electron conductive complex and flavins at high cell density, the EQS system dynamically switched the extracellular respiratory pathway of Shewanella oneidensis MR-1 according to cell density. The engineered strain exhibited precise switching and substantial improvement in the extracellular remediation of multiple nuclides, sequentially increasing the reduction of iodine IO 3 - and uranium U(VI) by 2.51- and 2.05-fold compared with the control, respectively. Furthermore, a mobile bacterial biofilm material was fabricated for collecting uranium precipitates coupled with U(VI) reduction. This work clearly demonstrates that EQS system contributes to the bidirectional regulation of EET pathway in EAB, providing an effective and refined strategy for bioremediation of multi-nuclide contamination. [Display omitted] • An EQS system was constructed for efficient gene expression and functional output. • Transmembrane pathway of S. oneidensis was dynamically controlled by EQS system. • The EQS system substantially promoted extracellular reduction of IO 3 - and U(VI). • Uranium precipitate was recovered along with U(VI) reduction by a biofilm material. [ABSTRACT FROM AUTHOR]

The gene encoding HIF‐2α, Epas1, has experienced a history of natural selection in many high‐altitude taxa, but the functional role of mutations in this gene is still poorly understood. We investigated the influence of the high‐altitude variant of Epas1 in North American deer mice (Peromyscus maniculatus) on the control of breathing and carotid body growth during chronic hypoxia. We created hybrids between high‐ and low‐altitude populations of deer mice to disrupt linkages between genetic loci so that the physiological effects of Epas1 alleles (Epas1H and Epas1L, respectively) could be examined on an admixed genomic background. In general, chronic hypoxia (4 weeks at 12 kPa O2) enhanced ventilatory chemosensitivity (assessed as the acute ventilatory response to hypoxia), increased total ventilation and arterial O2 saturation during progressive poikilocapnic hypoxia, and increased haematocrit and blood haemoglobin content across genotypes. However, the effects of chronic hypoxia on ventilatory chemosensitivity were attenuated in mice that were homozygous for the high‐altitude Epas1 allele (Epas1H/H). Carotid body growth and glomus cell hyperplasia, which was strongly induced in Epas1L/L mice in chronic hypoxia, was not observed in Epas1H/H mice. Epas1 genotype also modulated the effects of chronic hypoxia on metabolism and body temperature depression in hypoxia, but had no effects on haematological traits. These findings confirm the important role of HIF‐2α in modulating ventilatory sensitivity and carotid body growth in chronic hypoxia, and show that genetic variation in Epas1 is responsible for evolved changes in the control of breathing and metabolism in high‐altitude deer mice. Key points: High‐altitude natives of many species have experienced natural selection on the gene encoding HIF‐2α, Epas1, including high‐altitude populations of deer mice.HIF‐2α regulates ventilation and carotid body growth in hypoxia, and so the genetic variants in Epas1 in high‐altitude natives may underlie evolved changes in control of breathing.Deer mice from controlled crosses between high‐ and low‐altitude populations were used to examine the effects of Epas1 genotype on an admixed genomic background.The high‐altitude variant was associated with reduced ventilatory chemosensitivity and carotid body growth in chronic hypoxia, but had no effects on haematology.The results help us better understand the genetic basis for the unique physiological phenotype of high‐altitude natives. [ABSTRACT FROM AUTHOR]