Variable Physiological Conditions Research Articles

Physiological condition infers habitat choice in juvenile sockeye salmon.

The amount of time that juvenile salmon remain in an estuary varies among and within populations, with some individuals passing through their estuary in hours while others remain in the estuary for several months. Underlying differences in individual physiological condition, such as body size, stored energy and osmoregulatory function, could drive individual variation in the selection of estuary habitat. Here we investigated the role of variation in physiological condition on the selection of estuarine and ocean habitat by sockeye salmon (Oncorhynchus nerka) smolts intercepted at the initiation of their 650-km downstream migration from Chilko Lake, Fraser River, British Columbia (BC). Behavioural salinity preference experiments were conducted on unfed smolts held in fresh water at three time intervals during their downstream migration period, representing the stage of migration at lake-exit, and the expected timing for estuary-entry and ocean-entry (0, 1 and 3 weeks after lake-exit, respectively). In general, salinity preference behaviour varied across the three time periods consistent with expected transition from river to estuary to ocean. Further, individual physiological condition did influence habitat choice. Smolt condition factor (K) and energy density were positively correlated with salinity preference behaviour in the estuary and ocean outmigration stages, but not at lake-exit. Our results suggest that smolt physiological condition upon reaching the estuary could influence migratory behaviour and habitat selection. This provides evidence on the temporally dependent interplay of physiology, behaviour and migration in wild juvenile Pacific salmon, with juvenile rearing conditions influencing smolt energetic status, which in turn influences habitat choice during downstream migration. The implication for the conservation of migratory species is that the relative importance of stopover habitats may vary as a function of initial condition.

Application of biorelevant in vitro assays for the assessment and optimization of ASD-based formulations for pediatric patients

Amorphous solid dispersions (ASD) have been a successful formulation strategy to overcome the poor aqueous solubility of many novel drugs, but the development of pediatric formulations presents a special challenge due to variable gastrointestinal conditions in children. It was the aim of this work to design and apply a staged biopharmaceutical test protocol for the in vitro assessment of ASD-based pediatric formulations. Ritonavir was used as a model drug with poor aqueous solubility. Based on the commercial ASD powder formulation, a mini-tablet and a conventional tablet formulation were prepared. Drug release from the three formulations was studied in different biorelevant in vitro assays (i.e. MicroDiss, two-stage, transfer model, tiny-TIM) to consider different aspects of human GI physiology. Data from the two-stage and transfer model tests indicated that by controlled disintegration and dissolution excessive primary precipitation can be prevented. However, this advantage of the mini-tablet and tablet formulation did not translate into better performance in tiny-TIM. Here, the in vitro bioaccessibility was comparable for all three formulations. In the future, the staged biopharmaceutical action plan established herein will support the development of ASD-based pediatric formulations by improving the mechanistic understanding so that formulations are developed for which drug release is robust against variable physiological conditions.

Non-Invasive Electroretinogram Recording with Simultaneous Optogenetics to Dissect Retinal Ganglion Cells Electrophysiological Dynamics

Electroretinography (ERG) is a non-invasive electrophysiological recording technique that detects the electrical signaling of neuronal cells in the visual system. In conventional ERG recordings, the signals are considered a collective electrical response from various neuronal cell populations, including rods, cones, bipolar cells, and retinal ganglion cells (RGCs). However, due to the limited ability to control electrophysiological responses from different types of cells, the detailed information underlying ERG signals has not been analyzed and interpreted. Linking the features of ERG signals to the specific neuronal response will advance the understanding of neuronal electrophysiological dynamics and provide more evidence to elucidate pathological mechanisms, such as RGC loss during the progression of glaucoma. Herein, we developed an advanced ERG recording system integrated with a programmable, non-invasive optogenetic stimulation method in mice. In this system, we applied an automatic and unbiased ERG data analysis approach to differentiate a, b wave, negative response, and oscillatory potentials. To differentiate the electrophysiological response of RGCs in ERG recordings, we sensitized mouse RGCs with red-light opsin, ChRmine, through adeno-associated virus (AAV) intravitreal injection. Features of RGC dynamics under red-light stimulation were identified in the ERG readout. This non-invasive ERG recording system, associated with the programmable optogenetics stimulation method, provides a new methodology to dissect neural dynamics under variable physiological and pathological conditions in vivo. With the merits of non-invasiveness, improved sensitivity, and specificity, we envision this system can be further applied for early-stage detection of RGC degeneration and functional progression in neural degenerative diseases, such as glaucoma.

Characterization of structural features driving promiscuous ligand binding in GMCSF

Granulocyte macrophage colony stimulating factor (GMCSF) is a cytokine that is involved in myelopoiesis as well as immunomodulation. GMCSF has been shown to worsen conditions such as rheumatoid arthritis (RA) and multiple sclerosis (MS) while ameliorating diseases such as Type I Diabetes. GMCSF has also been used clinically to combat neutropenia based on its immunostimulatory activity. Pathophysiological properties of GMCSF have been highlighted by the incidence of the global pandemic, COVID‐19 (caused by SARS‐CoV‐2), where elevated levels of GMCSF were identified in COVID‐19 patients in cases related to development of systemic hyperinflammation, pneumonia and acute respiratory distress syndrome (ARDS). A key feature of signalling molecules like GMCSF is the selective and nuanced way in which responses can be tuned to external stimuli. The mechanism of how these signals are modulated are unknown and of particular interest. GMCSF and heparin have been shown to interact under low pH conditions. This binding interaction is important in two ways. Firstly, this pH sensitive interaction can serve as a basis to understand how cytokines can selectively interact with binding partners under variable physiological conditions. Secondly, in clinical settings where both anticoagulatory and immunostimulatory drugs are required, clear understanding of the binding interactions between the two drugs will help inform treatment decisions. Previously we identified heparin dependent structural changes as well as a striking dynamic change in GMCSF that was dependent on heparin chain length and pH using solution NMR studies which we believe to be dependent on a histidine triad. Here we have characterized GMCSF mutants using sited‐directed mutagenesis to exchange critical histidine residues for alternate amino acid residues (including Ala, Phe, Tyr and Asp) to probe the contributions of histidine residues to the increased flexibility of GMCSF observed in acidic conditions. We find that the histidine residues are critical for stability and as little as one amino acid difference will alter flexibility and stability of the protein. In some instances, mutations of all three histidine residues can lead to partial protein unfolding. Our results highlight the critical chemical properties at the amino acid level that allow GMCSF to interact with heparin in an environmentally dependent way.

Delivery of Potential Drugs to The Colon: Challenges and Strategies

Colon-targeted drug delivery systems have been exploited to treat local diseases in the colon, systemic delivery of protein and peptide, and chronotherapeutic drugs. The upper gastrointestinal tract restricts the effective delivery of these drugs. Therefore, several strategies are needed for targeted drugs directly to the colon, such as pH-sensitive polymers, enzyme-sensitive polymers, bacterially degradable polysaccharides, time-dependent polymers, and particulate systems. However, variable physiological conditions of the gastrointestinal tract in individuals cause combinations of these strategies are needed to ensure colonic delivery of the drug. This review presents and discusses several potential drugs and their approaches used to design and develop colon-targeted drug delivery systems for medications with particular characteristics.

132 Abundance and activity of metabolic enzymes in bovine cumulus cells derived from ovarian samples under variable physiological conditions.

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

The association between female reproductive performance and leukocyte telomere length in wild Soay sheep.

Telomere length (TL), typically measured across a sample of blood cells, has emerged as an exciting potential marker of physiological state and of the costs of investment in growth and reproduction within evolutionary ecology. While there is mounting evidence from studies of wild vertebrates that short TL predicts raised subsequent mortality risk, the relationship between reproductive investment and TL is less clear cut, and previous studies report both negative and positive associations. In this study, we examined the relationship between TL and different aspects of maternal reproductive performance in a free-living population of Soay sheep. We find evidence for shorter TL in females that bred, and thus paid any costs of gestation, compared to females that did not breed. However, we found no evidence for any association between TL and litter size. Furthermore, females that invested in gestation and lactation actually had longer TL than females who only invested in gestation because their offspring died shortly after birth. We used multivariate models to decompose these associations into among- and within-individual effects, and discovered that within-individual effects were driving both the negative association between TL and gestation, and the positive association between TL and lactation. This suggests that telomere dynamics may reflect recent physiologically costly investment or variation in physiological condition, depending on the aspect of reproduction being investigated. Our results highlight the physiological complexity of vertebrate reproduction, and the need to better understand how and why different aspects of physiological variation underpinning life histories impact blood cell TL.

Investigation on biofilm formation activity of Enterococcus faecium under various physiological conditions and possible application in bioremediation of tannery effluent

Treatment of tannery effluent (TE) using bacterial biofilm is a trending approach in the current scenario, due to greater survival and adaptation in stress conditions. The present study is concerned with the characterization of biofilm-forming bacterium Enterococcus faecium from tannery sludge and the investigation of their activity under different physiological conditions. Biofilm formation by E. faecium was strongly affected by variable physiological conditions. The optimum conditions were pH 7.5, temperature 28 °C, incubation time up to 96 h, glucose 1%, yeast extract 0.1–0.5%, NaCl 0.1–0.5%, tannery effluent-TE up to 50% v/v and Cd, Cr (VI) and Ni from 0.25 to 0.5 mM. Further, E. faecium treated TE was less phytotoxic on the fenugreek plant than the TE treated by non-biofilm forming isolate. The toxicity of TE could be reduced by the potentially biofilm-forming bacteria, which may be used in the bioremediation process.

Melatonin as a prospective metabolic regulator in pathologically altered cardiac energy homeostasis

A constant energy supply is indispensable for the relentlessly working heart. The unique metabolic flexibility of the cardiac tissue enables it to maintain its energy requirement under variable physiological conditions. However, some physiopathological statuses including aging, ischemia-reperfusion injury, diabetic cardiomyopathy, pathological cardiac hypertrophy, and heart failure frequently cause cardiac dysfunction and detrimental metabolic alteration. If the ATP supply fails to match the requirement of a working heart, the heart loses its functional capacity, resulting in slower recovery. A decrease in energy generation is often the ramifications of myocardial mitochondrial dysfunction and oxidative stress. Melatonin, a broad-spectrum antioxidant molecule has an appreciable role in the maintenance of metabolic homeostasis― from a single cell to an entire organism. Melatonin has the capacity to reduce ROS generation, preserve mitochondrial stability, and restore a robust mitochondrial function for unabated ATP production in cardiac tissues. Additionally, melatonin can promote carbohydrate and fat metabolism to further improve the ATP production in heart. In cardiac cells, melatonin upregulates GLUT4 expression either by impeding oxidative stress or by enhancing AMPK activation which accelerates fatty acid oxidation by upregulating PPAR-α and CPT-1α. Melatonin plays a pivotal role in the maintenance of calcium homeostasis in cardiomyocytes by obviating oxidative stress-mediated disruption of SERCA and NCX proteins. A possible role of melatonin to convert the Warburg effect to oxidative metabolism in pathological cardiac events has been recently contemplated. The current review will discuss the possible role of melatonin protecting against cardiac metabolic imbalances under pathological states.

Interplay of Adsorption, Supersaturation and the Presence of an Absorptive Sink on Drug Release from Mesoporous Silica-Based Formulations.

Mesoporous silica-based formulations of poorly soluble drugs may exhibit incomplete drug release due to drug remaining adsorbed on the silica surface. The goal of this study was (1) to evaluate the adsorption tendency of atazanavir from aqueous solution onto mesoporous silica (SBA-15) and (2) to determine if the drug release from mesoporous silica formulations was promoted by the presence of an absorptive compartment during dissolution testing. Atazanavir (ATZ) formulations with different drug loadings were prepared by incipient impregnation. The solid-state properties of the formulations were analyzed by X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared spectroscopy and thermogravimetric analysis. Drug release was compared for closed compartment versus absorptive dissolution testing at gastric and intestinal pH. XRD and DSC showed that all formulations were amorphous. Infrared spectra indicated intermolecular interactions between silanol groups in SBA-15 and carbonyl groups in atazanavir. Nanoconfinement of drug in silica mesopores was suggested by thermal analysis. Closed compartment dissolution testing showed incomplete drug release, largely due to theadsorption tendency of ATZ. However, coupled dissolution-absorption studies showed complete release over a 240min time period. This suggested that the depletion of drug in the dissolution medium due to drug diffusion across the membrane promotes drug release. Drug release was further improved when the formulation was first added to fasted state gastric pH conditions followed by pH-shift to intestinal conditions, which was attributed to the higher solubility of atazanavir at low pH. However, ATZ mesoporous silica formulations showed a poorer overall absorption behavior relative to a polymer-based amorphous solid dispersion formulation. This study highlights that absorptive dissolutionconditions promote drug desorption from the silica surface and hence, enhance drug release. Further, the influence of solution pH on drug release underscores the need to consider how variations in physiological conditions may impact the performance of mesoporous silica-based formulations. Graphical Abstract Drug release and adsorption tendency in the absence and presence of an absorptive sink during dissolution testing.

The biorelevant simulation of gastric emptying and its impact on model drug dissolution and absorption kinetics

The highly variable physiological conditions within the gastrointestinal tract can cause variable drug release and absorption from the orally administrated dosage forms. The emptying of the gastric content is one of the most critical physiological processes, dictating the amount of the active ingredient available for absorption into the systemic circulation. In this study, we prepared two water gastric emptying regimes on advanced gastric simulator (AGS) with programmable “pyloric” valve. Gastric emptying regimes were designed in such a way to capture the main findings of the MRI (magnetic resonance imaging) in vivo studies, conducted under fasted conditions according to the EMA and FDA guidelines for bioavailability and bioequivalence studies. Four immediate release formulations containing a model drug of BCS class III were tested. Comparative dissolution tests were also performed with the USP2 apparatus. In vitro release profiles were compared to the in vivo data in order to evaluate the importance of gastric emptying for subsequent absorption of the active substance from the tested formulations. Our bio-relevant in vitro dissolution model showed good discriminatory power for all of the tested formulations. Moreover, a better relation to in vivo data was achieved with AGS with respect to the tested conventional dissolution method.

Variations of Elastic Modulus and Cell Volume with Temperature for Cortical Neurons

Neurons change their growth dynamics and mechanical properties in response to external stimuli such as stiffness of the local microenvironment, ambient temperature, and biochemical or geometrical guidance cues. Here we use combined atomic force microscopy (AFM) and fluorescence microscopy experiments to investigate the relationship between external temperature, soma volume, and elastic modulus for cortical neurons. We measure how changes in ambient temperature affect the volume and the mechanical properties of neuronal cells at both the bulk (elastic modulus) and local (elasticity maps) levels. The experimental data demonstrate that both the volume and the elastic modulus of the neuron soma vary with changes in temperature. Our results show a decrease by a factor of 2 in the soma elastic modulus as the ambient temperature increases from room (25 °C) to physiological (37 °C) temperature, while the volume of the soma increases by a factor of 1.3 during the same temperature sweep. Using high-resolution AFM force mapping, we measure the temperature-induced variations within different regions of the elasticity maps (low and high values of elastic modulus) and correlate these variations with the dynamics of cytoskeleton components and molecular motors. We quantify the change in soma volume with temperature and propose a simple theoretical model that relates this change with variations in soma elastic modulus. These results have significant implications for understanding neuronal development and functions, as ambient temperature, cytoskeletal dynamics, and cellular volume may change with variations in physiological conditions, for example, during tissue compression and infections in vivo as well as during cell manipulation and tissue regeneration ex vivo.

Abstract 2655: Oxygen tension regulates lysosomal activation and receptor tyrosine kinase degradation

Abstract Oxygen sensing is crucial for adaptation to variable habitats and physiological conditions. Low oxygen tension, or hypoxia, is a common feature of solid tumors and hypoxic tumors are often more aggressive and resistant to therapy. Here we show that, in mammalian tissue culture cells, hypoxia suppressed lysosomal acidification/activation and receptor tyrosine kinase (RTK) degradation. Hypoxia down-regulated mTORc1, reducing its ability to activate transcription factor EB (TFEB), a master regulator of v-ATPase, the lysosomal proton pump. Hypoxia prevented epidermal growth factor receptor (EGFR) degradation in tumor tissues, whereas activation of lysosomes enhanced tumor cell response to anti-EGFR treatment. Our results linkoxygen tension and lysosomal activity, provide a molecular explanation of the malignant phenotype associated with hypoxic tumors, and suggest activation of lysosomes may provide therapeutic benefit in RTK-targeted cancer therapy. Citation Format: Jaewoo Hong, P. Charles Lin, Todd Wuest, Yongfen Min. Oxygen tension regulates lysosomal activation and receptor tyrosine kinase degradation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2655.

Statistical optimization of alginate-based oral dosage form of 5-aminosalicylic acid aimed to colonic delivery: In vitro and in vivo evaluation

Although different colon-targeting methods such as pH and time-dependent as well as bacterially degradable systems have been developed, due to variations in physiological conditions of patients, one system alone cannot produce a reliable drug delivery system. Therefore, in this study, an attempt was made to formulate 5-ASA pellets based on a combination of pH and time-dependent systems. A 32 full-factorial design was used to evaluate the effect of sodium alginate (SA) concentration and the polymer ratio (Eudragit® RS: Eudragit® S100) on morphology, mechanical features and release behaviour of 5-ASA pellet formulations. Fourier transform infrared spectroscopy, and differential scanning calorimetry analysis ruled out any interactions between the formulations components. The optimized formulation released 35, 55 and 89% of the drug within 15 h, at pHs 1.2, 6.8 and 7.4, respectively. In vivo studies demonstrated that the administration of sodium alginate-based matrix pellets containing 5-ASA coated with ES100 was effective in alleviating the damaged tissues and also decreased the inflammatory score and the rate of weight loss in colitis rats. The results indicated the remarkable anti-inflammatory efficacy of the designed colonic delivery system and the proposed formulations can be further developed in the pharmaceutical industry for patient use.

An oral drug delivery system with programmed drug release and imaging properties for orthotopic colon cancer therapy.

Oral drug delivery systems (ODDSs) have attracted considerable attention in relation to orthotopic colon cancer therapy due to certain popular advantages. Unfortunately, their clinical applications are generally limited by the side-effects caused by systemic drug exposure and poor real-time monitoring capabilities. Inspired by the characteristics of pH changes of the gastrointestinal tract (GIT) and specific enzymes secreted by the colonic microflora, we anchored polyacrylic acid (PAA) and chitosan (CS) on Gd3+-doped mesoporous hydroxyapatite nanoparticles (Gd-MHAp NPs) to realize programmed drug release and magnetic resonance imaging (MRI) at the tumor sites. In particular, the grafted PAA, as a pH-responsive switch, could effect controlled drug release in the colon. Further, CS is functionalized as the enzyme-sensitive moiety, which could be degraded by β-glycosidase in the colon. Gadolinium is a paramagnetic lanthanide element used in chelates, working as a contrast medium agent for an MRI system. Interestingly, after oral administration, CS and PAA could protect the drug-loaded nanoparticles (NPs) against variable physiological conditions in the GIT, allowing the drug to reach the colon tumor sites, preventing premature drug release. Enhanced drug concentrations at the colon tumor sites were achieved via this programmed drug release, which subsequently ameliorated the therapeutic effect. In addition, encapsulating both chemotherapeutic (5-fluorouracil, 5-FU) and targeted therapy drug (gefitinib, Gef) within Gd-MHAp NPs produced a synergistic therapeutic effect. In summary, this study demonstrated that such a novel drug system (Gd-MHAp/5-FU/Gef/CS/PAA NPs) could protect, transport, and program drug release locally within the colonic environment; further, this system exhibited a worthwhile therapeutic effect, providing a promising novel treatment strategy for orthotopic colon cancer.

Smart graphene-cellulose paper for 2D or 3D "origami-inspired" human stem cell support and differentiation.

Graphene-based materials represent advanced platforms for tissue engineering and implantable medical devices. From a clinical standpoint, it is essential that these materials are produced using non-toxic and non-hazardous methods, and have predictable properties and reliable performance under variable physiological conditions; especially when used with a cellular component. Here we describe such a biomaterial, namely smart graphene-cellulose (G-C) paper, and its suitability for traditional planar two-dimensional (2D) or three-dimensional (3D) human cell support, verified by adipose-derived stem cell (ADSC) culture and osteogenic differentiation. G-C paper is prepared using commercially available cellulose tissue paper as a substrate that is coated by immersion-deposition with graphene oxide (GO) followed by reduction to reduced graphene oxide (RGO) without the use of toxic organic solvents. The fabrication process is amenable to large scale production and the resultant papers have low electrical resistivity (up to ∼300 Ω/sq). Importantly, G-C papers can be configured to 3D constructs by lamination with alginate and further modified by folding and rolling for 3D "origami-inspired" cell-laden structures.

GPMVs in variable physiological conditions: could they be used for therapy delivery?

BackgroundCell based carriers are increasingly recognized as a good system for cargo delivery to cells. One of the reasons is their biocompatibility and low toxicity compared to artificial systems. Giant plasma membrane vesicles (GPMV) derive from the cell plasma membrane. Thus they offer the closest approximation to it, which makes them good candidates for potential drug delivery systems. To evaluate the applicability of GPMVs as carriers, we analyzed their basic biophysical properties to test their robustness in the face of changeable physiological conditions, as well as their ability to translocate across the membrane into cells.ResultsGPMVs formed from human umbilical vein endothelial cells (HUVEC) sustain a drastic osmotic challenge (50–500 mOsmoL/kg) unlike giant unilamelar vesicles (GUVs). In hyper-osmotic solutions the average volume decreases and membrane invaginations form, while in the hypo-osmolar buffer the volume of GPMVs increases and these changes were not reversible. The membranes of flaccid GPMVs started to wrinkle unevenly giving rise to buds after exposure to lipopolysaccharide (LPS). The shape changes in GUVs are reversible in contrast to GPMVs after LPS removal. GPMVs exposed to fluorescent LPS exhibited a signal that remained visible in some GPMVs even after LPS removal, which was never the case with GUVs. Calcein penetrated both into GUVs and GPMVs, however after the removal from the bulk solution some of the GPMVs still exhibited very bright signal, while in GUVs only a weak fluorescent signal was detected. We could also see that practically all GPMVs incorporated dextran initially, but after the dextran solution was changed with the initial non-fluorescent solution it remained only in 20% of them. The majority of HUVEC cells displayed a fluorescent signal after the incubation with GPMVs that contained fluorescently labeled dextran.ConclusionOur findings indicate that GPMVs behave quite differently from artificially made giant phospholipid vesicles and the changes induced by the different treatments we subjected them to are not reversible. We also demonstrate that different substances can be both loaded into them and delivered into cells, so GPMVs may be of potential use as cargo/therapy delivery systems.

Evaluation of venous blood gas levels, blood chemistry and haemocytometric parameters in milk fed veal calves at different periods of livestock cycle.

An evaluation of blood chemistry profile in relation to specific stages of livestock cycle can help better understand variations in physiological conditions in order to adjust management systems to animal needs. In addition to basal hematological investigation, the acid-base balance and blood gases are essential tools in evaluating metabolism in calves. The relationship between blood gas parameters, diet and growth should be further investigated. The aim of this study was to evaluate changes in acid-base status, blood gases, serum chemistry and hematological parameters in veal calves at different periods of livestock cycle. One hundred twenty-eight healthy cross breeding calves were enrolled in a farm in North-East Italy. Blood samplings were carried out from the jugular vein on day 1 (t1), 60 (t2) and 150 (t3) after arrival. Blood gas analysis was performed and hematological parameters were evaluated. One-way ANOVA and Tukey-Kramer post-hoc test were performed to assess differences between blood parameter values at the different periods. The main differences in blood gas parameter levels during the livestock cycle concerned pH, Base Excess and HCO3 with higher values recorded in t3. Urea, creatinine, gamma-glutamyl transpeptidase and bilirubin mean values were significantly higher in t1 than in t2 and t3. Aspartate aminotransferase increased from t1 to t2 and t3. Alkaline Phosphatase was higher in t2. Fe levels severely dropped in t2 and in t3, and the decrease led to a restrained but significant reduction in haemoglobin values. A correspondent decrease in the other haemocytometric parameters was found.

High Pressure and [Ca 2+ ] Produce an Inverse Modulation of Synaptic Input Strength and Network Excitability in the Rat Dentate Gyrus.

Hyperbaric environments induce the high pressure neurological syndrome (HPNS) characterized by hyperexcitability of the central nervous system (CNS) and memory impairment. Human divers and other animals experience the HPNS at pressures beyond 1.1 MPa. High pressure depresses synaptic transmission and alters its dynamics in various animal models. Medial perforant path (MPP) synapses connecting the medial entorhinal cortex with the hippocampal formation are suppressed by 50% at 10.1MPa. Reduction of synaptic inputs is paradoxically associated with enhanced ability of dentate gyrus (DG)’ granule cells (GCs) to generate spikes at high pressure. This mechanism allows MPP inputs to elicit standard GC outputs at 0.1–25 Hz frequencies under hyperbaric conditions. An increased postsynaptic gain of MPP inputs probably allows diving animals to perform in hyperbaric environments, but makes them vulnerable to high intensity/frequency stimuli producing hyperexcitability. Increasing extracellular Ca2+ ([Ca2+]o) partially reverted pressure-mediated depression of MPP inputs and increased MPP’s low-pass filter properties. We postulated that raising [Ca2+]o in addition to increase synaptic inputs may reduce network excitability in the DG potentially improving its function and reducing sensitivity to high intensity and pathologic stimuli. For this matter, we activated the MPP with single and 50 Hz frequency stimuli that simulated physiologic and deleterious conditions, while assessing the GC’s output under various conditions of pressure and [Ca2+]o. Our results reveal that the pressure and [Ca2+]o produce an inverse modulation on synaptic input strength and network excitability. These coincident phenomena suggest a potential general mechanism of networks that adjusts gain as an inverse function of synaptic inputs’ strength. Such mechanism may serve for adaptation to variable pressure and other physiological and pathological conditions and may explain the increased sensitivity to strong sensory stimulation suffered by human deep-divers and cetaceans under hyperbaric conditions.

WITHIN-SEASON STABILITY OF STRAWBERRY SOLUBLE SOLIDS CONTENT IN FLORIDA

Several studies have documented significant variation in the soluble solids content (SSC) of strawberries (Fragaria x ananassa) during Florida's growing season. This fluctuation may result from variable physiological and environmental conditions interacting throughout the season. Cultivars with SSC stability would be valued in the commercial industry due to their more uniform quality. The stability of 385 genotypes from the strawberry breeding program at the University of Florida was estimated using the approach from Finlay and Wilkinson (1963). For each genotype a linear regression of SSC against the mean SSC of an independent set of genotypes at each harvest date was calculated. The magnitude of the slopes was considered an estimate of each genotype's stability. The means at each harvest date reflect the combined effects of physiological and environmental conditions that were common to all genotypes and served as estimates of how favorable conditions were for SSC during the relevant interval prior to harvest. Genotypes with steep slopes are sensitive to small changes in field conditions and are considered unstable compared to genotypes with slopes close to zero. Slopes ranged from flat to almost two times steeper than the population's value. About 87% of genotypes had average stability, whereas 7% were classified as unstable and the remaining 6% was considered stable. Results revealed that the within-season stability of SSC, as measured in this study, is a trait that shows significant variation across genotypes in the strawberry breeding program at the University of Florida. The analysis presented here is a starting point for understanding the genetic control of SSC stability. The repeatability of these results across different seasons has not yet been tested and will be examined in the future.