Physiological Mechanisms Research Articles

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.

The tetraploid wheat (Triticum dicoccum (Schrank) Schuebl.) improves nitrogen uptake and assimilation adaptation to nitrogen-deficit stress.

The genetic diversity in tetraploid wheat provides a genetic pool for improving wheat productivity and environmental resilience. The tetraploid wheat had strong N uptake, translocation, and assimilation capacity under N deficit stress, thus alleviating growth inhibition and plant N loss to maintain healthy development and adapt to environments with low N inputs. Tetraploid wheat with a rich genetic variability provides an indispensable genetic pool for improving wheat yield. Mining the physiological mechanisms of tetraploid wheat in response to nitrogen (N) deficit stress is important for low-N-tolerant wheat breeding. In this study, we selected emmer wheat (Kronos, tetraploid), Yangmai 25 (YM25, hexaploid), and Chinese spring (CS, hexaploid) as materials. We investigated the differences in the response of root morphology, leaf and root N accumulation, N uptake, translocation, and assimilation-related enzymes and gene expression in wheat seedlings of different ploidy under N deficit stress through hydroponic experiments. The tetraploid wheat (Kronos) had stronger adaptability to N deficit stress than the hexaploid wheats (YM25, CS). Kronos had better root growth under low N stress, expanding the N uptake area and enhancing N uptake to maintain higher NO3- and soluble protein contents. Kronos exhibited high TaNRT1.1, TaNRT2.1, and TaNRT2.2 expression in roots, which promoted NO3- uptake, and high TaNRT1.5 and TaNRT1.8 expression in roots and leaves enhanced NO3- translocation to the aboveground. NR and GS activity in roots and leaves of Kronos was higher by increasing the expression of TANIA2, TAGS1, and TAGS2, which enhanced the reduction and assimilation of NO3- as well as the re-assimilation of photorespiratory-released NH4+. Overall, Kronos had strong N uptake, translocation, and assimilation capacity under N deficit stress, alleviating growth inhibition and plant N loss and thus maintaining a healthy development. This study reveals the physiological mechanisms of tetraploid wheat that improve nitrogen uptake and assimilation adaptation under low N stress, which will provide indispensable germplasm resources for elite low-N-tolerant wheat improvement and breeding.

Three concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance

Heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Heteroresistance reduces treatment efficacy across diverse bacterial species and antibiotic classes, yet its genetic and physiological mechanisms remain poorly understood. Here, we investigated a multi-resistant Klebsiella pneumoniae isolate and identified three primary drivers of gene dosage-dependent heteroresistance for several antibiotic classes: tandem amplification, increased plasmid copy number, and transposition of resistance genes onto cryptic plasmids. All three mechanisms imposed fitness costs and were genetically unstable, leading to fast reversion to susceptibility in the absence of antibiotics. We used a mouse gut colonization model to show that heteroresistance due to elevated resistance-gene dosage can result in antibiotic treatment failures. Importantly, we observed that the three mechanisms are prevalent among Escherichia coli bloodstream isolates. Our findings underscore the necessity for treatment strategies that address the complex interplay between plasmids, resistance cassettes, and transposons in bacterial populations.

Neuro-fascial-vascular training for the treatment of Raynaud's phenomenon: a case report.

Primary Raynaud's phenomenon is characterized by episodic, reversible, and disabling vasospasms of the peripheral arteries. In the most severe cases, it can lead to ulceration of the fingers and toes. Neurofascial Vascular Training (NFVT) is a novel therapeutic approach for treating primary Raynaud's phenomenon (PRP). NFVT aims to enhance peripheral circulation and stimulate the autonomic nervous system (ANS) by engaging multiple physiological mechanisms simultaneously. This integrated approach works to reduce vasospasms and alleviate associated symptoms through neurodynamic and myofascial interventions. A 54-year-old woman, who has experienced pain and hypoesthesia in her hands for nine years, received a diagnosis of PRP without systemic sclerosis in 2014. The patient reported daily colour changes in her fingers, along with pain and a temporary decrease in tactile sensitivity. The patient engaged in ten 30-minute exercise sessions, and the clinical outcomes were assessed based on several parameters. These included the frequency and duration of vasospastic attacks, evaluated using the Raynaud Condition Score, as well as pain and tingling, measured through the daily Numeric Rating Scale (NRS). The Composite Autonomic Symptom Score (COMPASS 31) was utilized to assess dysautonomia, while the frequency of medication use and the DASH questionnaire were also considered. The results indicated a significant improvement in symptoms. Conclusion: NFVT improved symptoms and motor dysfunction in a patient with Raynaud's syndrome, demonstrating how NFVT can increase peripheral blood flow, stimulate the ANS, and improve symptoms in PRP.

Multiomic Signatures of Traffic-Related Air Pollution in London Reveal Potential Short-Term Perturbations in Gut Microbiome-Related Pathways.

This randomized crossover study investigated the metabolic and mRNA alterations associated with exposure to high and low traffic-related air pollution (TRAP) in 50 participants who were either healthy or were diagnosed with chronic pulmonary obstructive disease (COPD) or ischemic heart disease (IHD). For the first time, this study combined transcriptomics and serum metabolomics measured in the same participants over multiple time points (2 h before, and 2 and 24 h after exposure) and over two contrasted exposure regimes to identify potential multiomic modifications linked to TRAP exposure. With a multivariate normal model, we identified 78 metabolic features and 53 mRNA features associated with at least one TRAP exposure. Nitrogen dioxide (NO2) emerged as the dominant pollutant, with 67 unique associated metabolomic features. Pathway analysis and annotation of metabolic features consistently indicated perturbations in the tryptophan metabolism associated with NO2 exposure, particularly in the gut-microbiome-associated indole pathway. Conditional multiomics networks revealed complex and intricate mechanisms associated with TRAP exposure, with some effects persisting 24 h after exposure. Our findings indicate that exposure to TRAP can alter important physiological mechanisms even after a short-term exposure of a 2 h walk. We describe for the first time a potential link between NO2 exposure and perturbation of the microbiome-related pathways.

Histone modifications affecting plant dormancy and dormancy release: common regulatory effects on hormone metabolism.

As sessile organisms, plants enter periods of dormancy in response to environmental stresses to ensure continued growth and reproduction in future. During dormancy, plant growth is suppressed, adaptive/survival mechanisms are exerted, and stress tolerance increases over a prolonged period until the plants resume their development or reproduction under favorable conditions. In this review, we focus on seed dormancy and bud dormancy, which are critical for adaptations to fluctuating environmental conditions. We provide an overview of the physiological characteristics of both types of dormancy as well as the importance of the phytohormones abscissic acid and gibberellin for establishing and releasing dormancy, respectively. Additionally, recent epigenetic analyses have revealed that dormancy establishment and release are associated with the removal and deposition of histone modifications at the loci of key regulatory genes influencing phytohormone metabolism and signaling, including DELAY OF GERMINATION 1 and DORMANCY-ASSOCIATED MADS-box genes. We discuss our current understanding of the physiological and molecular mechanisms required to establish and release seed dormancy and bud dormancy, while also describing how environmental conditions control dormancy depth, with a focus on the effects of histone modifications.

P21/Zbtb18 repress the expression of cKit to regulate the self-renewal of hematopoietic stem cells.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.

Exploring the genetic control of sweat gland characteristics in beef cattle for enhanced heat tolerance

BackgroundThermal stress in subtropical regions is a major limiting factor in beef cattle production systems with around $369 million being lost annually due to reduced performance. Heat stress causes numerous physiological and behavioral disturbances including reduced feed intake and decreased production levels. Cattle utilize various physiological mechanisms such as sweating to regulate internal heat. Variation in these traits can help identify genetic variants that control sweat gland properties and subsequently allow for genetic selection of cattle with greater thermotolerance.MethodsThis study used 2,401 Brangus cattle from two commercial ranches in Florida. Precise phenotypes that contribute to an animal’s ability to manage heat stress were calculated from skin biopsies and included sweat gland area, sweat gland depth, and sweat gland length. All animals were genotyped with the Bovine GGP F250K, and BLUPF90 software was used to estimate genetic parameters and for Genome Wide Association Study.ResultsSweat gland phenotypes heritability ranged from 0.17 to 0.42 indicating a moderate amount of the phenotypic variation is due to genetics, allowing producers the ability to select for favorable sweat gland properties. A weighted single-step GWAS using sliding 10 kb windows identified multiple quantitative trait loci (QTLs) explaining a significant amount of genetic variation. QTLs located on BTA7 and BTA12 explained over 1.0% of genetic variance and overlap the ADGRV1 and CCDC168 genes, respectively. The variants identified in this study are implicated in processes related to immune function and cellular proliferation which could be relevant to heat management. Breed of Origin Alleles (BOA) were predicted using local ancestry in admixed populations (LAMP-LD), allowing for identification of markers’ origin from either Brahman or Angus ancestry. A BOA GWAS was performed to identify regions inherited from particular ancestral breeds that might have a significant impact on sweat gland phenotypes.ConclusionsThe results of the BOA GWAS indicate that both Brahman and Angus alleles contribute positively to sweat gland traits, as evidenced by favorable marker effects observed from both genetic backgrounds. Understanding and utilizing genetic traits that confer better heat tolerance is a proactive approach to managing the impacts of climate change on livestock farming.

Peripheral 5-HT mediates GnIH-induced feeding behavior and energy metabolism disorder in chickens via the 5-HT2C receptor.

Gonadotropin-inhibitory hormone (GnIH) plays a critical role of reproduction in vertebrate since its discovery. Recently, a regulatory role of GnIH in appetite and the energy metabolism has emerged, despite its precise physiological mechanisms remain unknown. Thus, the present study evaluated the effects of a single or long-term GnIH treatments (administered via intraperitoneal injection) on the food intake, weight and glucolipid metabolism of chickens, while investigated the possible neuroendocrinology factors and its mechanism that involved in GnIH-induced obesity and glucolipid metabolism disorder. Our results showed that the intraperitoneal administration of GnIH to chickens resulted in marked body mass increased, hyperlipidemia, hyperglycemia and glucose intolerance. Subsequently, the results of metabolomics and pharmacological inhibition of 5-HT2C receptor studies revealed that blocked 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight and the levels of blood glucose and lipid, resulted in GnIH-induced hyperglycaemia, hyperlipidemia and hepatic lipid deposition even worse, suggesting that peripheral 5-HT via 5-HT2C receptor may act as a negative feedback regulator to interplay with GnIH and jointly homeostatic control of energy balance in chickens. Our present study provide evidence of the cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level and to propose a molecular basis for these interactions, suggesting that functional interaction between GnIH and 5-HT may open new avenues to understand the mechanism of neuroendocrine network involved in appetite and energy metabolism as well as provide a new therapeutic strategy to prevent obesity, diabetes and metabolic disorders.

Herbicide safener isoxadifen-ethyl associated with increased Goss's wilt severity in corn (Zea mays).

Goss's bacterial wilt and leaf blight (Goss's wilt), caused by the bacterium Clavibacter nebraskensis, is a corn disease that has been a top ten yield-reducing disease in North America in the past 15 years. Isoxadifen-ethyl is an herbicide safener that effectively increases cytochrome P450 activity in corn which enhances a plant's metabolism of herbicide molecules. Recent research found a potential link between isoxadifen-ethyl and increased Goss's wilt severity. The application of isoxadifen-ethyl increased (P = 0.014-0.046) area under disease progress curve (AUDPC) by 19%, 7%, and 9% at three environments, independent of accompanying herbicide or herbicide application timing. However, no significant differences in incidence of systemic wilt or corn grain yield occurred among treatments at any environment. These data provide evidence for an association between isoxadifen-ethyl safener and Goss's wilt in corn. The reason for this association is unknown, but the safener may affect plant or pathogen physiological mechanisms. While the increased disease severity did not result in decreased grain yield in these experiments, an increase in pathogen inoculum due to higher disease severity could influence Goss' wilt epidemics in future years. © 2024 Society of Chemical Industry.

Utilizing machine learning to facilitate the early diagnosis of posterior circulation stroke

BackgroundPosterior Circulation Syndrome (PCS) presents a diagnostic challenge characterized by its variable and nonspecific symptoms. Timely and accurate diagnosis is crucial for improving patient outcomes. This study aims to enhance the early diagnosis of PCS by employing clinical and demographic data and machine learning. This approach targets a significant research gap in the field of stroke diagnosis and management.MethodsWe collected and analyzed data from a large national Stroke Registry spanning from January 2014 to July 2022. The dataset included 15,859 adult patients admitted with a primary diagnosis of stroke. Five machine learning models were trained: XGBoost, Random Forest, Support Vector Machine, Classification and Regression Trees, and Logistic Regression. Multiple performance metrics, such as accuracy, precision, recall, F1-score, AUC, Matthew’s correlation coefficient, log loss, and Brier score, were utilized to evaluate model performance.ResultsThe XGBoost model emerged as the top performer with an AUC of 0.81, accuracy of 0.79, precision of 0.5, recall of 0.62, and F1-score of 0.55. SHAP (SHapley Additive exPlanations) analysis identified key variables associated with PCS, including Body Mass Index, Random Blood Sugar, ataxia, dysarthria, and diastolic blood pressure and body temperature. These variables played a significant role in facilitating the early diagnosis of PCS, emphasizing their diagnostic value.ConclusionThis study pioneers the use of clinical data and machine learning models to facilitate the early diagnosis of PCS, filling a crucial gap in stroke research. Using simple clinical metrics such as BMI, RBS, ataxia, dysarthria, DBP, and body temperature will help clinicians diagnose PCS early. Despite limitations, such as data biases and regional specificity, our research contributes to advancing PCS understanding, potentially enhancing clinical decision-making and patient outcomes early in the patient’s clinical journey. Further investigations are warranted to elucidate the underlying physiological mechanisms and validate these findings in broader populations and healthcare settings.

Electrosensory and metabolic responses of weakly electric fish to changing water conductivity.

Weakly electric Gymnotiform fishes use self-generated electric organ discharges (EODs) to navigate and communicate. The electrosensory range for these processes is a function of EOD amplitude, determined by the fish's electric organ (EO) output and the electrical conductivity of the surrounding water. Anthropogenic activity, such as deforestation, dams, and industrial/agricultural runoff, are known to increase water conductivity in neotropical habitats, likely reducing the electrosensory range of these fish. We investigated whether fish modulate EO output as means of re-expanding electrosensory range after a rapid increase in water conductivity in the pulse-type Brachyhypopomus gauderio and the wave-type Eigenmannia virescens. Furthermore, because EOD production incurs significant metabolic costs, we assessed whether such compensation is associated with an increase in metabolic rate. Following the conductivity increase B. gauderio increased EOD amplitude by 20.2±4.3% over six days but with no associated increase in metabolic rate, whereas the EOD amplitude of E. virescens remained constant, accompanied by an unexpected decrease in metabolic rate. Our results suggest that B. gauderio uses a compensation mechanism that requires no metabolic investment, such as impedance matching, or a physiological tradeoff wherein energy is diverted from other physiological processes to increase EO output. These divergent responses between species could be the result of differences in reproductive life history or evolutionary adaptations to different aquatic habitats. Continued investigation of electrosensory responses to changing water conditions will be essential for understanding the effects of anthropogenic disturbances on gymnotiforms, and potential physiological mechanisms for adapting to a rapidly changing aquatic environment.

Gamma-aminobutyric acid (GABA) improves salinity stress tolerance in soybean seedlings by modulating their mineral nutrition, osmolyte contents, and ascorbate-glutathione cycle

BackgroundIn plants, GABA plays a critical role in regulating salinity stress tolerance. However, the response of soybean seedlings (Glycine max L.) to exogenous gamma-aminobutyric acid (GABA) under saline stress conditions has not been fully elucidated.ResultsThis study investigated the effects of exogenous GABA (2 mM) on plant biomass and the physiological mechanism through which soybean plants are affected by saline stress conditions (0, 40, and 80 mM of NaCl and Na2SO4 at a 1:1 molar ratio). We noticed that increased salinity stress negatively impacted the growth and metabolism of soybean seedlings, compared to control. The root-stem-leaf biomass (27- and 33%, 20- and 58%, and 25- and 59% under 40- and 80 mM stress, respectively]) and the concentration of chlorophyll a and chlorophyll b significantly decreased. Moreover, the carotenoid content increased significantly (by 35%) following treatment with 40 mM stress. The results exhibited significant increase in the concentration of hydrogen peroxide (H2O2), malondialdehyde (MDA), dehydroascorbic acid (DHA) oxidized glutathione (GSSG), Na+, and Cl− under 40- and 80 mM stress levels, respectively. However, the concentration of mineral nutrients, soluble proteins, and soluble sugars reduced significantly under both salinity stress levels. In contrast, the proline and glycine betaine concentrations increased compared with those in the control group. Moreover, the enzymatic activities of ascorbate peroxidase, monodehydroascorbate reductase, glutathione reductase, and glutathione peroxidase decreased significantly, while those of superoxide dismutase, catalase, peroxidase, and dehydroascorbate reductase increased following saline stress, indicating the overall sensitivity of the ascorbate-glutathione cycle (AsA-GSH). However, exogenous GABA decreased Na+, Cl−, H2O2, and MDA concentration but enhanced photosynthetic pigments, mineral nutrients (K+, K+/Na+ ratio, Zn2+, Fe2+, Mg2+, and Ca2+); osmolytes (proline, glycine betaine, soluble sugar, and soluble protein); enzymatic antioxidant activities; and AsA-GSH pools, thus reducing salinity-associated stress damage and resulting in improved growth and biomass. The positive impact of exogenously applied GABA on soybean plants could be attributed to its ability to improve their physiological stress response mechanisms and reduce harmful substances.ConclusionApplying GABA to soybean plants could be an effective strategy for mitigating salinity stress. In the future, molecular studies may contribute to a better understanding of the mechanisms by which GABA regulates salt tolerance in soybeans.

Energetic cost of biosynthesis is a missing link between growth and longevity in mammals

The comparative studies of aging have established a negative correlation between Gompertz postnatal growth constant and maximum lifespan across mammalian species, but the underlying physiological mechanism remains unclear. This study shows that the Gompertz growth constant can be decomposed into two energetic components, mass-specific metabolic rate and the energetic cost of biosynthesis, and that after controlling the former as a confounder, the negative correlation between growth constant and lifespan still exists due to a 100-fold variation in the latter, revealing that the energetic cost of biosynthesis is a link between growth and longevity in mammals. Previously, the energetic cost of biosynthesis has been thought to be a constant across species and therefore was not considered a contributor to the variation in any life history traits, such as growth and lifespan. This study employs a recently proposed model based on energy conservation to explain the physiological effect of the variation in this energetic cost on the aging process and illustrates its role in linking growth and lifespan. The conventional life history theory suggested a tradeoff between growth and somatic maintenance, but the findings in this study suggest that allocating more energy to biosynthesis may enhance the somatic maintenance and extend lifespan and, hence, reveal a more complex nature of the tradeoff.

Beyond Obesity and Overweight: The Clinical Assessment and Treatment of Excess Body Fat in Children : Part 1 - Insulin Resistance as the Root Cause of Pediatric Obesity.

Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

Beyond Obesity and Overweight: the Clinical Assessment and Treatment of Excess Body Fat In Children : Part 2 - the Prescription of Low-Carbohydrate Eating as the First Approach.

Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

PSV-21 Pediococcus acidilactici survives an in vitro simulated digestion

Abstract In the swine industry, probiotics are recognized for optimizing growth performance and production efficiency by modulating host physiology, and the response across studies is not consistent. One area of focus is probiotic mitigation of post-weaning diarrhea, and further mechanistic understanding of probiotic and host physiology could help with consistent performance outcomes. An essential attribute of a probiotic is the ability to survive the harsh environments of the gastrointestinal tract (GIT). The aim of this study was to determine if Pediococcus Acidilactici PECh3A (PA) that has been previously genome sequenced for determining gut physiology mechanisms can survive an in vitro simulated digestion. In the in vitro digestion PA concentrations that were investigated included 108, 109, and 1010 colony forming units (CFU)/mL. The in vitro digestion (n = 4/concentration) consisted of 5 phases with incubation times simulating the GIT; initial inoculation (0 h), gastric (2 h), upper intestinal (4 h), lower intestinal (9 h) and extended lower intestinal phase (9 h). For the initial inoculation concentrations of PA were added into 25 mL of sterile milk replacer representing dietary requirements of a suckling pig. In the gastric phase pepsin was added and pH was adjusted to 2.5. In the upper intestinal phase bile and pancreatin were added, along with a pH adjustment to 6.8. In the lower intestinal phase, the multi-enzyme complex consisting of carbohydrase enzymes was added and pH adjusted to 4.8. There was no addition during the extended lower intestinal phase. At each sample collection at the end of a phase 1 mL was collected from each flask. For each sample, 100 µL were serially diluted, plated on deMan, Rogosa, and Sharpe (MRS) plates, and incubated at 37°C for 24h. Survivability was determined by counting CFUs and comparing the concentration with the initial CFU/mL at 0 h and reported as percent survival (%S). Data for the in vitro digestion were analyzed according to a randomized complete block design (RCBD) in a split plot using the Repeated Measures Glimmix Procedure of SAS. Additional orthogonal contrasts were analyzed across PA concentrations. Data showed survival for 108,109, and 1010CFU/mL at all sample phases (108 - 44.24, 60.14, 58.36, 55.69%S; 109 - 40.56, 55.60, 49.35, 50.7%S; 1010 - 32.98, 52.55, 46.72, 43.71%S ± 2.98 respectively; phase P < 0.01 and concentration P < 0.01). There is evidence of a phase and concentration effect on survivability, but no interaction. A linear concentration response was observed across concentrations (54.61, 49.05, 43.99%S ± 1.23; P < 0.05) indicating that as concentration increases the survivability decreases. These findings indicate that PA PECh3A can survive a simulated GIT and potentially impact swine intestinal physiology.

Behavioral Interventions Can Improve Brain Injury-Induced Deficits in Behavioral Flexibility and Impulsivity Linked to Impaired Reward-Feedback Beta Oscillations.

Traumatic brain injury (TBI) affects a large population, resulting in severe cognitive impairments. Although cognitive rehabilitation is an accepted treatment for some deficits, studies in patients are limited in ability to probe physiological and behavioral mechanisms. Therefore, animal models are needed to optimize strategies. Frontal TBI in a rat model results in robust and replicable cognitive deficits, making this an ideal candidate for investigating various behavioral interventions. In this study, we report three distinct frontal TBI experiments assessing behavior well into the chronic post-injury period using male Long-Evans rats. First, we evaluated the impact of frontal injury on local field potentials recorded simultaneously from 12 brain regions during a probabilistic reversal learning (PbR) task. Next, a set of rats were tested on a similar PbR task or an impulsivity task (differential reinforcement of low-rate behavior [DRL]) and half received salient cues associated with reinforcement contingencies to encourage engagement in the target behavior. After intervention on the PbR task, brains were stained for markers of activity. On the DRL task, cue relevance was decoupled from outcomes to determine if beneficial effects persisted on impulsive behavior. TBI decreased the ability to detect reinforced outcomes; this was evident in task performance and reward-feedback signals occurring at beta frequencies in lateral orbitofrontal cortex (OFC) and associated frontostriatal regions. The behavioral intervention improved flexibility and increased OFC activity. Intervention also reduced impulsivity, even after cues were decoupled, which was partially mediated by improvements in timing behavior. The current study established a platform to begin investigating cognitive rehabilitation in rats and identified a strong role for dysfunctional OFC signaling in probabilistic learning after frontal TBI.

A comprehensive evaluation of different responses of supplementary light qualities on physiological and biochemical mechanisms of ‘Kyoho’ grape

Grape is an economically important fruit crop worldwide, for which light qualities play a diverse role in vineyard growth and development. However, the regulatory mechanisms between different light qualities and the quality of plant growth at the morphophysiological and pomological levels remain unknown. Therefore, in the current study, we studied plant physiological, biochemical and genetical analysis to investigate the response of all seven light qualities, including red (R), blue (B), white (W), 1-red, 1 blue (1R1B), 2-red, 1-blue (2R1B), 1-red, 2-blue (1R2B), and natural (N, was used as control group) to evaluate ‘Kyoho'grape (Vitis labrusca L. × V. vinifera) morphophysiological, pomological traits at light responsive transcriptional pathway, which revealed the possible networking metabolism controlling fruit quality and quantity of grape plant. Our results showed that photosynthetic indicators such as leaf stomata, number of stomata, and longitudinal and transverse diameter of stomata improved under red and blue light qualities as compared to white light. Leaf gas exchange indicators showed that net photosynthetic rate, transpiration rate, intercellular CO2 concentration rate, total conductance to CO2, stomatal conductance, conductance to water vapor, maximal quantum yield of PS (II), actual photochemical quantum efficiency, electron transfer chain, and non-photochemical quantum efficiency improve under blue and red light. Photosynthetic pigments showed that chlorophyll a and b, carotenoid, and total pigment contents improved under blue and red light. Nutrient elements showed that potassium, phosphorous, magnesium, calcium, iron, and zinc contents improved under blue and red light. Morphological and organic acid indicators such as the appearance of fruit shape, firmness, and titratable acidity improved under blue and light. However, there was a notable increment in the total soluble sugar under blue and red light as compared to natural light. The composition of sugar including (sucrose, fructose, glucose) and organic acids (tartaric acid, citric acid, and malic acid) improved under blue and red light (fruits) and showed notable reductions for tartaric acid under blue and red light (leaves) as compared to natural light. Aromatic compounds showed that esters, aldehydes, acetaldehyde, 2-hexenal, ethyl acetate, n-propyl acetate, butanoic acid, ethyl ester, 1-hexanol, 2-ethyl, 2-propanone, and 1‑hydroxyl, improved under blue and red light. Further, changes in enhanced expression of light-responsive genes including VvCRYI, VvCRY2, VvPHYA, VvPHYB, VvCOP1, VvHY5, VvHYH, and VvPIF4 upregulated under blue and red light, while VvPIF3.1 down-regulated as compared to natural light. Also, chlorophyll synthesis-related genes including VvSGR, VvPAO, and VvCHLH upregulated under blue and red light, while VvNYC1, VvPPH, and VvPOR showed noticeable changes under blue and red light as compared to natural light. Interestingly, most of the relative genes were highly expressed in fruits as compared to leaves. Finally, we have established correlation and principal component analysis for indicators in grapes. Current findings provide novel mechanisms by which different responses of supplementary light control the plant fruit quality of grapes.

Excess Intramyocellular Lipid Does Not Affect Muscle Fiber Biophysical Properties in Mice or People with Metabolically Abnormal Obesity.

Observational studies show correlations between intramyocellular lipid (IMCL) content and muscle strength and contractile function in people with "metabolically abnormal" obesity. However, a clear physiologic mechanism for this association is lacking and causation is debated. We combined immunofluorescent confocal imaging with force measurements on permeabilized muscle fibers from metabolically normal and metabolically abnormal mice and metabolically normal (defined as normal fasting plasma glucose and glucose tolerance) and metabolically abnormal (defined as pre-diabetes and type 2 diabetes) people with overweight/obesity to evaluate relationships among myocellular lipid droplet characteristics (droplet size and density) and biophysical (active contractile and passive viscoelastic) properties. The fiber type specificity of lipid droplet parameters varied between metabolically abnormal and normal mice and among metabolically normal and metabolically abnormal people. However, despite considerable quantities of IMCL in the metabolically abnormal groups, there were no significant differences in peak active tension or passive viscoelasticity between the metabolically abnormal groups and the control group in mice or people. Additionally, there were no significant relationships among IMCL parameters and biophysical variables. Thus, we conclude that IMCL accumulation per se does not impact muscle fiber biophysical properties or physically impede contraction.