Adaptive Physiological Responses Research Articles

Brainwave Patterns and Metabolic Adaptations in Rowers Crossing the Atlantic: A Case Series Pilot Study.

This pilot study was designed to test the hypothesis that quantitative electroencephalographic (qEEG) measurements reflect physiological adaptations for brain energy reallocation. The study focused on a team of three well-matched male rowers participating in a 30-day, 2,650-mile continuous transatlantic rowing competition, examining the effects of extreme, prolonged stress on brain function and metabolic adaptations. Measurements at the start and finish lines included body weight, height, waist circumference, body fat, and a panel of hormones and biochemical markers. Post-race qEEG parameters were recorded under eyes-open (EO) and eyes-closed (EC) conditions. qEEG data were compared to a reference population (ages 6-90 years) and to an age-matched 27-year-old male medical student serving as a control subject. qEEG analysis evaluated voltage amplitudes, wave distribution patterns, theta-to-beta ratios (TBR), and coherence levels. Hormonal changes and oxidative stress markers were also assessed before and after race. Two rowers exhibited post-race dominance of high-frequency beta activity, while one displayed co-dominance of delta and beta waves. Compared to the control subject (TBR = 1.25), the rowers' low TBRs (< 0.2) indicated high vigilance and low relaxation during EC conditions. Cortisol levels increased in all rowers and were associated with beta coherence >1 SD above the reference mean. Testosterone decreased in two rowers but increased in one; the smallest cortisol increase corresponded with the largest testosterone decrement. Decreases in oxidative stress markers correlated with a shift from right- to left-sided alpha asymmetry, consistent with redistribution of alpha wave energy to the nondominant hemisphere. This pattern was also observed in the control subject. Increased testosterone in one rower was linked to a decrease in the percentage of sites exhibiting normal theta frequencies, indicating a potential role for testosterone in brain energy reallocation. The findings suggest that qEEG measurements reflect physiological adaptations in response to extreme stress, supporting the hypothesis that metabolic energy is reallocated to optimize vigilance and performance. The observed correlations between hormonal changes, oxidative stress markers, and qEEG parameters provide preliminary evidence of mechanisms for brain energy reallocation. These insights highlight the potential for qEEG to identify biomarkers of stress adaptation and lay the groundwork for larger studies to further elucidate these mechanisms.

Shaping cardiac destiny: the role of post-translational modifications on endoplasmic reticulum - mitochondria crosstalk in cardiac remodeling.

Cardiac remodeling is a shared pathological change in most cardiovascular diseases. Encompassing both adaptive physiological responses and decompensated pathological changes. Anatomically, atrial remodeling is primarily caused by atrial fibrillation, whereas ventricular remodeling is typically induced by myocardial infarction, hypertension, or cardiomyopathy. Mitochondria, the powerhouse of cardiomyocytes, collaborate with other organelles such as the endoplasmic reticulum to control a variety of pathophysiological processes such as calcium signaling, lipid transfer, mitochondrial dynamics, biogenesis, and mitophagy. This mechanism is proven to be essential for cardiac remodeling. Post-translational modifications can regulate intracellular signaling pathways, gene expression, and cellular stress responses in cardiac cells by modulating protein function, stability, and interactions, consequently shaping the myocardial response to injury and stress. These modifications, in particular phosphorylation, acetylation, and ubiquitination, are essential for the regulation of the complex molecular pathways that underlie cardiac remodeling. This review provides a comprehensive overview of the crosstalk between the endoplasmic reticulum and mitochondria during cardiac remodeling, focusing on the regulatory effects of various post-translational modifications on these interactions.

Investigating the Impact of Fasting and Refeeding on Blood Biochemical Indicators and Transcriptional Profiles in the Hypothalamus and Subcutaneous Adipose Tissue in Geese.

Fasting and refeeding systems can cause significant short-term fluctuations in nutrient and energy levels, triggering adaptive physiological responses in animals. This study examines the effects of fasting and refeeding on blood biochemical indicators and transcriptional profiles in the hypothalamus and subcutaneous adipose tissue of geese. Biochemical assays reveal that fasting significantly increases levels of free fatty acids and glucagon, while reducing concentrations of triglycerides, leptin, and insulin. Transcriptomic analyses identify a complex transcriptional response in both the hypothalamus and subcutaneous adipose tissue, affecting several metabolic pathways and key genes associated with feed intake and energy metabolism. In subcutaneous adipose tissue, fasting downregulates genes involved in fatty acid synthesis (LPL, SCD, and ACSL1) and upregulates PLIN2, a gene promoting lipid droplet degradation. Fasting affects a variety of metabolic pathways and critical genes in the hypothalamus, including Apelin, insulin, and mTOR signaling pathways. After fasting, the mRNA expression of NOG, GABRD, and IGFBP-1 genes in the hypothalamus are significantly upregulated, while proopiomelanocortin (POMC) gene expression is markedly downregulated. This study highlights the intricate biological responses to nutritional changes in geese, which adds to our understanding of energy balance and metabolic regulation in avian species.

RNA-seq reveals the important role of transcriptional regulator DeoR1 in regulating Brucella abortus various pathways

Brucella spp. is an intracellular bacterium that uses its transcriptional regulator DeoR1 to promote intracellular transport and survival, but the molecular mechanism remains unknown. To analyze the role of DeoR1 in the virulence of B. abortus and the genes regulated by DeoR1, we created a A19ΔdeoR1 mutant of B. abortus A19 (A19). Virulence assay was performed using a murine macrophage cell line (RAW264.7) and mice. We observed that A19ΔdeoR1 mutant is attenuated in RAW264.7 cells and mice. We performed RNA-seq whole transcriptome analysis of A19ΔdeoR1 and A19 from infected RAW264.7 cells. A total of 135 differentially expressed genes were identified, including 100 up-regulated and 35 down-regulated genes. These differentially expressed genes were involved in amino acid synthesis and metabolism, energy production and conversion, stress proteins, chaperonin, hypothetical proteins and protein of unknown function, cell wall/membrane/envelope, intracellular transporting and secretion, and transcriptional regulator. Interestingly, genes involved in the intracellular trafficking and secretion were significantly down-regulated in A19ΔdeoR1. Furthermore, selected RNA-seq results were experimentally confirmed by qRT-PCR. Overall, these results deciphered differential phenomena associated with virulence in A19ΔdeoR1 and A19 from infected RAW264.7 cells, which provided important information for understanding the detailed role of DeoR1 in Brucella pathogenesis. SignificanceTranscriptional regulators are predominant bacterial signal transduction factors. The pathogenicity of Brucella is due to its ability to regulate the expression of virulence related genes. Transcriptional regulators are designed to regulate gene expression and enact an appropriate adaptive physiological response. Here, a total of 135 differentially expressed genes were identified in transcriptional regulator deoR1 mutant.

Transcriptome Analysis Reveals the Regulatory Mechanism of Lipid Metabolism and Oxidative Stress in Litopenaeus vannamei under Low-Salinity Stress

Salinity is a crucial environmental factor influencing the survival, growth, development, and reproduction of aquatic animals. However, the underlying molecular mechanisms of the shrimp’s response to salinity stress are not yet fully understood. Therefore, we used the Illumina NovaSeq 6000 platform to perform transcriptome sequencing of the hepatopancreas of Litopenaeus vannamei under high-salinity (30 PSU), medium-salinity (10 PSU), and low-salinity (0.5 PSU) conditions. We obtained 63.23 Gb of high-quality data and identified 3589 differentially expressed genes (DEGs), including 1638 upregulated and 1951 downregulated genes. Notably, a comparison between the control group (30 PSU) and the low-salinity group (0.5 PSU) revealed that the BBOX1 and CHE1 genes were significantly upregulated, while the ACOX1, MPV, CYP2L1, GCH, MVK, TREt1, and XDH genes were significantly downregulated. These genes are primarily involved in key metabolic pathways, such as fatty acid oxidation, cholesterol metabolism, and hormone synthesis and metabolism. The key genes involved in fatty acid β-oxidation, such as ACOX1, ACAD, HADH, HSD17B4, PECR, CROT, PIPOX, and CG5009, all showed a downward trend, suggesting that L. vannamei may respond to salt stress by regulating fatty acid oxidative metabolism, optimizing energy utilization, and maintaining cell homeostasis under low-salinity conditions. Functional annotation of gene ontology (GO) and KEGG pathway enrichment analysis highlighted the roles of these significant DEGs in the adaptation of L. vannamei to environments of varying salinity, underscoring the importance of metabolic pathways in their adaptive physiological responses. This study provides a crucial molecular biological basis for understanding the molecular mechanisms and physiological protection strategies of L. vannamei under salinity stress.

Translational insights into the hormetic potential of carbon dioxide: from physiological mechanisms to innovative adjunct therapeutic potential for cancer.

Carbon dioxide (CO2), traditionally viewed as a mere byproduct of cellular respiration, plays a multifaceted role in human physiology beyond simple elimination through respiration. CO2 may regulate the tumor microenvironment by significantly affecting the release of oxygen (O2) to tissues through the Bohr effect and by modulating blood pH and vasodilation. Previous studies suggest hypercapnia (elevated CO2 levels) might trigger optimized cellular mechanisms with potential therapeutic benefits. The role of CO2 in cellular stress conditions within tumor environments and its impact on O2 utilization offers a new investigative area in oncology. This study aims to explore CO2's role in the tumor environment, particularly how its physiological properties and adaptive responses can influence therapeutic strategies. By applying a structured translational approach using the Work Breakdown Structure method, the study divided the analysis into six interconnected work packages to comprehensively analyze the interactions between carbon dioxide and the tumor microenvironment. Methods included systematic literature reviews, data analyses, data integration for identifying critical success factors and exploring extracellular environment modulation. The research used SMART criteria for assessing innovation and the applicability of results. The research revealed that the human body's adaptability to hypercapnic conditions could potentially inform innovative strategies for manipulating the tumor microenvironment. This could enhance O2 utilization efficiency and manage adaptive responses to cellular stress. The study proposed that carbon dioxide's hormetic potential could induce beneficial responses in the tumor microenvironment, prompting clinical protocols for experimental validation. The research underscored the importance of pH regulation, emphasizing CO2 and carbonic acid's role in modulating metabolic and signaling pathways related to cancer. The study underscores CO2 as vital to our physiology and suggests potential therapeutic uses within the tumor microenvironment. pH modulation and cellular oxygenation optimization via CO2 manipulation could offer innovative strategies to enhance existing cancer therapies. These findings encourage further exploration of CO2's therapeutic potential. Future research should focus on experimental validation and exploration of clinical applications, emphasizing the need for interdisciplinary and collaborative approaches to tackle current challenges in cancer treatment.

Non-invasive determination of critical dissolved oxygen thresholds for stress physiology in fish using triple-oxygen stable isotopes and aquatic respirometry

ABSTRACT Understanding the critical thresholds of dissolved oxygen (O2) that trigger adaptive physiological responses in aquatic organisms is long hampered by a lack of robust, non-lethal or non-invasive methodologies. The isotope fractionation of triple O2 isotopes (18O/17O/16O) during respiration is linked to the amount of oxygen utilised, offering a potential avenue for new insights. Our experimental research involved measuring the oxygen isotope fractionation of dissolved O2 in closed-system aquatic respirometry experiments with wild sticklebacks (Gasterosteus aculeatus). These fish were either naturally adapted or experimentally acclimated to hypoxic and normoxic conditions. The aim was to observe their oxygen usage and isotope fractionation in response to increasingly severe hypoxia. Initial observations revealed a progressive 18O enrichment from the preferential uptake of 16O to a dissolved oxygen threshold of 3–5 mg O2 L–1, followed by an apparent reversal in oxygen isotope fractionation, which is mixing of 16O and 17O with the remaining O2 pool across all populations and indicative of a systematic change in oxygen metabolism among the fish. Unexpectedly, sticklebacks adapted to hypoxia but acclimated to normoxia exhibited stronger oxygen isotope fractionation compared to those adapted to normoxia and acclimated to hypoxia, contradicting the hypothesis that hypoxia adaptation would lead to reduced isotope discrimination due to more efficient oxygen uptake. These preliminary experimental results highlight the novel potential of using dissolved O2 isotopes as a non-invasive, non-lethal method to quantitatively assess metabolic thresholds in aquatic organisms. This approach could significantly improve our understanding of the critical oxygen responses and adaptation mechanisms in fish and other aquatic organisms across different oxygen environments, marking a significant step forward in aquatic ecological and physiological research.

Effluents from a university clinical analysis teaching laboratory: an inductive study on adhesion and cellular response of Pseudomonas aeruginosa

Microbial resistance to antibiotics is a global threat and the World Health Organization (WHO) predicts that future pandemics will involve resistant microorganisms. Recently, the WHO published a list of pathogenic microbes whose priority level varies among medium, high and critical. All bacteria in the list can form biofilms. Biofilms are structures made of polymeric adhesive matrix composed by multispecies in close association. Additionally, biofilm provides an important physical barrier. Different phenotypes are found in biofilms, ensuring resistance to oxidative stress, as well as environmental stress factors. It results cell persistence because there is generation of a gradient of chemical inhibitors at subinhibitory levels, which promote the development of resistant subpopulations able to grow and disseminate. Clinical analysis laboratories are sources of selective pressures for potentially pathogenic bacteria because different substances are handled and discarded daily by the effluents generated. This study assessed the activity of a highly toxic leachate on isolates of Pseudomonas aeruginosa recovered from the sinks of a university clinical analysis teaching laboratory. In vitro biofilm formation tests, pyocyanin quantification, cell wall hydrophobicity test, motility test and susceptibility to seven antibiotics were carried out. The isolate with the most antibiotic resistance was assessed. There was a reduction in adhesion of 14 to 430%. Biofilm was formed, however, on all tested materials; the cells preferentially adhered to hydrophilic surfaces, dolomite, followed by galvanized iron and glass. Maximum pyocyanin production was 12 mM. Swimming motility was stimulated, recording a 12-fold increase in speed, while swarming and twitching motility were inhibited by around 20 and 60%, respectively. All isolates were resistant to cephalosporins and one isolate was detected resistant also to ciprofloxacin. The results indicated that P. aeruginosa survived the leachate, triggering different adaptive physiological responses to persist in the stressful environment.

Summatory Effects of Anaerobic Exercise and a 'Westernized Athletic Diet' on Gut Dysbiosis and Chronic Low-Grade Metabolic Acidosis.

Anaerobic exercise decreases systemic pH and increases metabolic acidosis in athletes, altering the acid-base homeostasis. In addition, nutritional recommendations advising athletes to intake higher amounts of proteins and simple carbohydrates (including from sport functional supplements) could be detrimental to restoring acid-base balance. Here, this specific nutrition could be classified as an acidic diet and defined as 'Westernized athletic nutrition'. The maintenance of a chronic physiological state of low-grade metabolic acidosis produces detrimental effects on systemic health, physical performance, and inflammation. Therefore, nutrition must be capable of compensating for systemic acidosis from anaerobic exercise. The healthy gut microbiota can contribute to improving health and physical performance in athletes and, specifically, decrease the systemic acidic load through the conversion of lactate from systemic circulation to short-chain fatty acids in the proximal colon. On the contrary, microbial dysbiosis results in negative consequences for host health and physical performance because it results in a greater accumulation of systemic lactate, hydrogen ions, carbon dioxide, bacterial endotoxins, bioamines, and immunogenic compounds that are transported through the epithelia into the blood circulation. In conclusion, the systemic metabolic acidosis resulting from anaerobic exercise can be aggravated through an acidic diet, promoting chronic, low-grade metabolic acidosis in athletes. The individuality of athletic training and nutrition must take into consideration the acid-base homeostasis to modulate microbiota and adaptive physiological responses.

Variation in photosynthetic capacity of Salvia przewalskii along elevational gradients on the eastern Qinghai-Tibetan Plateau, China

Elevational variation in plant growing environment drives diversification of photosynthetic capacity, however, the mechanism behind this reaction is poorly understood. We measured leaf gas exchange, chlorophyll fluorescence, anatomical characteristics, and biochemical traits of Salvia przewalskii at elevations ranging from 2400 m to 3400 m above sea level (a.s.l) on the eastern Qinghai-Tibetan Plateau, China. We found that photosynthetic capacity showed an initial increase and then a decrease with rising elevation, and the best state observed at 2800 m a.s.l. Environmental factors indirectly regulated photosynthetic capacity by affecting stomatal conductance (gs), mesophyll conductance (gm), maximum velocity of carboxylation (Vc max), and maximum capacity for photosynthetic electron transport (Jmax). The average temperature (T) and total precipitation (P) during the growing season had the highest contribution to the variation of photosynthetic capacity of S. przewalskii in subalpine areas, which were 25% and 24%, respectively. Photosynthetic capacity was mainly affected by diffusional limitations (71%–89%), and mesophyll limitation (lm) played a leading role. The variation of gm was attributed to the effects of environmental factors on the volume fraction of intercellular air space (fias), the thickness of cell wall (Tcw), the surface of mesophyll cells and chloroplasts exposed to intercellular airspace (Sm, Sc), and plasma membrane intrinsic protein (PIPs, PIP1, PIP2), independent of carbonic anhydrase (CA). Optimization of leaf tissue structure and adaptive physiological responses enabled plants to efficiently cope with variable climate conditions of high-elevation areas, and the while maintaining high levels of carbon assimilation.

Houttuynia cordata Thunb: Ethnobotanical and availability notes in the Cu Chi district, Vietnam

Houttuynia cordata, a plant with a long history of traditional medicinal and culinary uses across different cultures, has shown effectiveness in treating various ailments in Southeast Asia. The Cu Chi district of southern Vietnam, is home to 35 out of the country's 54 ethnic minority groups, making it an ideal location to investigate the traditional uses and availability of H. cordata within the local community. The study findings reveal notable differences in leaf anatomy, thickness, and vascular bundles, which can be attributed to variations in soil conditions. The Phu My Hung area, characterized by lower soil moisture and nutrient content, indicates more pronounced drought conditions. H. cordata from this region exhibits higher antioxidant capacity and develops lignified cells as an adaptation to dry conditions, thereby enhancing water use efficiency. The findings of this study highlight the significant implications of the distinct populations of H. cordata belonging to the same species. These populations have undergone morphological and physiological adaptations in response to their specific ecological conditions. Notably, the H. cordata population from drought-prone areas such as Phu My Hung exhibits remarkable potential for medicinal applications. This suggests that the unique environmental pressures in these regions have influenced the plant's composition and properties, making it a valuable resource for medicinal research and potential therapeutic developments. The identification and utilization of such adaptations in H. cordata populations could have far-reaching implications in the field of medicine, offering new avenues for drug discovery and the treatment of various ailments.

Elevated blood pressure follows physiological body-water conservation

Background: Pre-clinical evidence suggests that blood pressure (BP) increase is part of an adaptive physiological body response designed to prevent under-hydration. This idea challenges established thinking that hypertension is caused by initial salt-driven over-hydration. We tested the hypothesis that this alternative view also holds true in humans. Methods: In a mechanistic study, we investigated the interrelation between daily Na+ and water intake, renal solute and water excretion, renal water conservation, and body Na+ balance with BP in 6 healthy men living in a controlled environment for 205 days. In an additional daily-life observational study we investigated the interrelation between BP and adaptive-physiological water and Na+ conservation in 108 Singaporeans. Results: In participants living under controlled conditions, BP increased when urine osmolality was high, and fluid intake or urine volume was low. This BP-increasing water conservation response was not caused by body Na+ retention. Similarly, participants living under daily-life conditions showed a BP-elevating adaptive body water conservation response with increased plasma solute concentration, increased plasma vasopressin levels, and reduced urine volume production due to reduced renal free-water excretion. Participants with higher BP relied on more urea and glucose solutes, but on less Na+ solutes, to maintain their hydration status. Participants with essential hypertension showed more pronounced adaptive-physiological water conservation. None of these hypertension-specific water conservation responses were accompanied by differences in 24-h Na+ excretion. Conclusions: BP increase in humans is part of a systemic body water conservation response that occurs largely independent of body Na+ balance. The Mars500 Salt and Water Homeostasis Project was realized by grant support from the German Federal Ministry for Economics and Technology/DLR Forschung unter Weltraumbedingungen (50WB1624-50WB2024) and the Interdisciplinary Centre for Clinical Research (IZKF Junior Research Group 2), Friedrich-Alexander-University of Erlangen-Nuremberg to JT. The food products were donated by APETITO, Coppenrath und Wiese, ENERVIT, HIPP, Katadyn, Kellogg, Molda, and Unilever. The Sodium Storage in Singaporeans Project was realized with grant support from Duke NUS Medical School (Duke-NUS-KBrFA/2019/0026) to JT. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney.

Tissue regeneration is limited in several organs, including the kidney, contributing to the high prevalence of kidney disease globally. However, evolutionary and physiological adaptive responses and the presence of renal progenitor cells suggest an existing remodeling capacity. This study uncovered endogenous tissue remodeling mechanisms in the kidney that were activated by the loss of body fluid and salt and regulated by a unique niche of a minority renal cell type called the macula densa (MD). Here, we identified neuronal differentiation features of MD cells that sense the local and systemic environment and secrete angiogenic, growth, and extracellular matrix remodeling factors, cytokines and chemokines, and control resident progenitor cells. Serial intravital imaging, MD nerve growth factor receptor and Wnt mouse models, and transcriptome analysis revealed cellular and molecular mechanisms of these MD functions. Human and therapeutic translation studies illustrated the clinical potential of MD factors, including CCN1, as a urinary biomarker and therapeutic target in chronic kidney disease. The concept that a neuronally differentiated key sensory and regulatory cell type responding to organ-specific physiological inputs controls local progenitors to remodel or repair tissues may be applicable to other organs and diverse tissue-regenerative therapeutic strategies.

Clinical challenges in asymptomatic chronic aortoiliac occlusive disease

Asymptomatic aortoiliac occlusive disease, while less common compared to other peripheral arterial diseases, presents unique clinical challenges. Our center recently encountered a case involving a patient with chronic occlusion of the distal abdominal aorta and bilateral iliac arteries. Remarkably, this patient had developed an extensive network of collateral circulation, effectively compensating for the reduced blood supply to the pelvic and lower limb areas. This adaptive physiological response resulted in the patient exhibiting no significant clinical symptoms. To reveal the most effective diagnostic and treatment strategies for asymptomatic peripheral artery disease patients to avoid complications and other challenges, more clinical studies are needed in the future.

Human Understanding is Expected of the Physician: Proposing a Model of Disease Development

In Harrison’s Principles of Internal Medicine, human understanding is emphasized as one of three necessary characteristics that a physician must have. Inflammation, which is caused by inflammatory inducers (inf-ids), is a fundamental feature of disease at the cellular and molecular levels. Inflammation protects the body, but excessive or prolonged inflammation can be damaging and can cause disease. Humans are repeatedly exposed to external and internal environmental factors that generate inf-ids throughout their lives. External environmental factors include microbial and non-microbial inf-ids, as well as stressors that inevitably arise during social interactions. Internal environmental factors include the adaptive physiological response that is present from birth. Inf-ids may also be produced by the four-step habit loop, which consists of a cue (e.g., stressor), emotions, routine act (adaptive response), and a reward. Immune cells in the circulatory system and in tissues may have positive and negative effects in inflammatory responses. However, low-grade inflammation may be difficult to detect. We propose a model of disease development that integrates external and internal environmental factors from the perspective of human understanding.

Eco-Physiological Studies of Some Halophytes Naturally Occurring in Tehsil Deedwana, District Deedwana-Kuchaman, Rajasthan, India

Abstract: Deedwana tehsil of State Rajasthan is facing a tragic problem of salinity. Almost 60% of total 160252.99 ha of land is under salt stress. This has created a deleterious impact on, not only the soils of these lands but also on the yield of the crops therein. Eco-physiological studies of some halophytes of these areas have shown that there are very characteristic structural features have been developed in these plants. Possible factor for this is soil which undergoing degradation due to increased ionic levels. This research paper presents an eco-physiological investigation of three halophytes, Salsola baryosma, Suaeda fruticosa, and Trianthema triquetra, in the arid region of Deedwana, Rajasthan, India. The study aims to understand the adaptive strategies and physiological responses of these plants to the extreme salinity conditions prevailing in their habitat. Field surveys were conducted to assess the distribution and abundance of the selected halophytes, followed by collection of plant samples for laboratory analysis.

Abstract 392: MYB regulates a specific subset of hypoxia-induced genes and exhibits altered genomic occupancy under hypoxia

Abstract Hypoxia, an unavoidable microenvironmental stress, greatly influences the tumor cell behavior and therapeutic outcomes. Under low oxygen condition, tumor cells undergo transcriptional reprogramming, largely mediated through hypoxia-inducible factors (HIFs), triggering adaptive response pathways. We recently demonstrated a significant role of MYB in hypoxic survival of pancreatic cancer cells by facilitating adaptive changes in cellular metabolism in collaboration with HIF1α. Here, we employed genome-wide deep sequencing approaches to study the impact of hypoxia on transcriptional reprogramming of pancreatic cancer cells and investigate the role of MYB in the hypoxia-dependent processes. A large number of differentially expressed genes (DEGs) were identified in pancreatic cancer cells subjected to hypoxia (1% O2) and associated with multiple adaptive response pathways. Specifically, we found that pathways related to autophagy, cell migration, epithelial-to-mesenchymal transition, endocytosis, cytoskeleton reorganization were induced, while those associated with RNA processing, ribosome biogenesis, DNA replication and cell cycle were suppressed. To analyze the role of MYB in these adaptive responses, we compared the relative abundance of transcripts in MYB-overexpressing control and MYB knockout (KO) pancreatic cancer cells when cultured under normoxic or hypoxic conditions. We observed that the transcriptional output of MYB was drastically changed under hypoxia with a vast majority of genes being distinctly altered in response to the loss of MYB expression under normoxia and hypoxia. To examine if it resulted from altered genomic occupancy of MYB under normoxia and hypoxia, we compared MYB ChIP-seq peaks under these conditions. We observed a decrease in overall MYB-bound genomic regions under hypoxia despite the fact that we did not observe a decrease in nuclear MYB expression. More interestingly, the genomic occupancy of MYB shifted substantially from regions proximal to transcription start site to distal intergenic or intronic regions under hypoxia. Studies are currently underway to examine the mechanisms underlying the altered MYB genomic occupancy and its impact on adaptive physiological response of pancreatic cancer cells under hypoxia. Together, our findings bring unprecedented insight into the mechanistic role of MYB in hypoxia adaptation and pancreatic cancer pathobiology. Citation Format: Shashi Anand, Mohammad Aslam Khan, Kunwar Somesh Vikramdeo, Seema Singh, Ajay Pratap Singh. MYB regulates a specific subset of hypoxia-induced genes and exhibits altered genomic occupancy under hypoxia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 392.

Assessing safety, efficacy and residue depletion in golden mahseer, Tor putitora (Hamilton, 1822): biochemical and physiological responses to graded concentrations of oxytetracycline dietary supplementation.

The safety and effectiveness of oxytetracycline can potentially manage bacterial infections in fish. This, in turn, might reduce the concerns related to its use in aquaculture and human consumption, such as toxicity, antimicrobial resistance, and other associated risks. The primary objective of this study was to assess how adding oxytetracycline dihydrate to the diet affects its effectiveness, safety, and the presence of residues in T. putitora. T. putitora fingerlings, subjected to experimental infection with Aeromonas hydrophila at a concentration of 108 CFU mL- 1, received an oral administration of oxytetracycline dihydrate. The oxytetracycline dihydrate was added to the feed (corresponding to 2% of the fish body weight) at concentrations of 44.1, 88.2, 132.3 and 176.4mg Kg- 1 fish body weight per day. This treatment was carried out for 10 consecutive days. The biochemical and physiological responses of T. putitora and efficacy of oxytetracycline dihydrate were determined through estimation of microbial load (CFU mL- 1), haematogram, serum biomarkers, behavioral characteristics, non-specific immunity and residue depletion. Experimentally infected fish showed disease progression and induced histopathological conditions with highest microbial load (CFU mL- 1) in the muscle of both control and treated fish. The fish haematogram showed increased leucocyte and haemoglobin content, influenced by dietary oxytetracycline dihydrate. The fish demonstrated adaptive physiological response to oxytetracycline dihydrate at 44.1 to 88.2mg and resulted in increased albumin and globulin content. The serum-enzyme assay showed significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and plasma alkaline phosphatase (ALP) activities in the test fish (< 0.05). Oxytetracycline dihydrate at 88.2 to 132.3mg Kg- 1 fish body weight per day recorded higher feed intake (75%), significant survivability (66-68%) and histopathological recovery. The suppressed immune response was manifested with decreased respiratory burst and lysozyme activity. The palatability, treatment of bacterial infection, histopathological changes and survivability by fingerlings of golden mahseer determined the safety and optimized the therapeutic potential of the oxytetracycline dihydrate at 88.2mg Kg- 1 fish body weight per day for 10 days to contain the infection by A. hydrophila. A withdrawal period of 8-d was recommended as oxytetracycline dihydrate concentration depleted below the legal maximum residue limit (MRL 2.0 mg g- 1) in the edible muscle of the golden mahseer reared at an average water temperature of 20°C. This is considered safe for human consumption.

In Silico Modeling and Validation of the Effect of Calcium-Activated Potassium Current on Ventricular Repolarization in Failing Myocytes.

The pathophysiological role of the small conductance calcium-activated potassium (SK) channels in human ventricular myocytes remains unclear. Experimental studies have reported upregulation of in pathological states, potentially contributing to ventricular arrhythmias. In heart failure (HF) patients, the upregulation of SK channels could be an adaptive physiological response to shorten the action potential duration (APD) under conditions of reduced repolarization reserve. In this work, we aimed at uncovering the contribution of SK channels to ventricular repolarization in failing myocytes. We extended an in silico electrophysiological model of human ventricular failing myocytes by including a representation of the SK channel activity. To calibrate the maximal SK current conductance (G SK), we simulated action potentials (APs) at different pacing frequencies and matched the changes in AP duration induced by SK channel inhibition or activation to available experimental data. The optimal value obtained for GSK was 4.288 μ S/ μF in mid-myocardial cells, and 6.4 μS/ μF for endocardial and epicardial cells. The simulated SK block-induced effects were consistent with experimental evidence. 1-D simulations of a transmural ventricular fiber indicated that SK channel block may prolong the QT interval and increase the transmural dispersion of repolarization, potentially increasing the risk of arrhythmia in HF. Our results highlight the importance of considering the SK channels to improve the characterization of HF-induced ventricular remodeling. Simulations across various scenarios in 0-D and 1-D scales suggest that pharmacological SK channel inhibition could lead to adverse effects in failing ventricles.

The Role of Stress Modifier Biostimulants on Adaptive Strategy of Oregano Plant for Increasing Productivity under Water Shortage.

To investigate the influence of stress modulators on the adaptive physiological responses and biomass traits of oregano under water stress conditions, a two-year (2018 and 2019) randomized complete block-designed factorial research was performed. In this study, oregano plants were treated with five stress modulators levels (CHN: chitosan, AMA: amino acids, SEW: seaweed, ASA: ascorbic acid, SAA: salicylic acid, and CON: control) at three levels of irrigation regimes (Irr40 (40), Irr60 (60) and Irr75 (75) % field capacity). The effects of water shortage and biostimulant application were evaluated on total dry weight (TDW), relative water content (RWC), essential oil production, chlorophyll, nutrient (N, K, and P), proline, total soluble sugar, polyphenol and flavonoid content, and activity of antioxidant enzymes. The result showed that under optimal irrigation conditions, oregano plants sprayed with CHN exhibited the highest dry weight (141.23 g m-2) as a morphological trait, the highest relative water content (79.34%), the most consistent concentrations of nitrogen, phosphorus and potassium (3.14, 0.39, and 1.69%, respectively), chlorophylls a and b (3.02 and 1.95 mg g-1 FW, respectively), and total phenols and total flavonoids (30.72 and 3.17 mg g-1 DW, respectively). The water deficit increased the proline content, with the greatest amount (4.17 μg g-1 FW) observed in control plants. Moreover, under moisture shortage stress conditions, the application of CHN and SEW increased the soluble sugar (27.26 μmol g-1 FW) and essential oil yield (1.80%) production, the catalase, ascorbate peroxidase, and superoxide dismutase activities (3.17, 1.18, and 63.89 μmol min-1 g-1 FW, respectively) compared to control plants. In summary, the study demonstrated that oregano plants respond positively to stress modulator treatments when subjected to moisture shortage stress, especially when treated with chitosan. The results offer promising insights for developing sustainable adaptative strategies aimed at enhancing the oregano's tolerance to water shortage, ultimately improving its productivity and biochemical traits.