Autoregulated and Non-Autoregulated Blood Flow Restriction on Acute Arterial Stiffness.

This study aimed to investigate the acute effects of autoregulated and non-autoregulated applied pressures during blood flow restriction resistance exercise to volitional fatigue on indices of arterial stiffness using the Delfi Personalized Tourniquet System. Following a randomized autoregulated or non-autoregulated blood flow restriction familiarization session, 20 physically active adults (23±5 years; 7 females) participated in three randomized treatment-order sessions with autoregulated and non-autoregulated and no blood flow restriction training. Participants performed four sets of dumbbell wall squats to failure using 20% of one repetition maximum. Blood flow restriction was performed with 60% of supine limb occlusion pressure. Testing before and post-session included an ultrasonic scan of the carotid artery, applanation tonometry, and blood pressure acquisition.Carotid-femoral pulse wave velocity increased in the non-autoregulated and no blood flow restriction training groups following exercise while carotid-radial pulse wave velocity increased in the no blood flow restriction training group (all p<0.05). Carotid-femoral pulse wave velocity exhibited an interaction effect between autoregulated and non-autoregulated blood flow restriction in favor of autoregulated blood flow restriction (p<0.05). Autoregulated blood flow restriction training does not influence indices of arterial stiffness while non-autoregulated and no blood flow restriction training increases central stiffness.

Sprint Interval Training on Stationary Air Bike Elicits Cardiorespiratory Adaptations While Being Time-Efficient.

ABSTRACT: Moghaddam, M, Cervantes, M, Cheshier, B, and Jacobson, BH. Sprint interval training on stationary air bike elicits cardiorespiratory adaptations while being time-efficient. J Strength Cond Res 37(9): 1795-1801, 2023-Sprint interval training (SIT) refers to a set of brief intermittent exercises that are performed at maximal intensity. This study compared the effects of 2 SIT protocols (e.g., 10-5-SIT and 20-10-SIT) vs. moderate-intensity continuous training (MICT) on cardiovascular adaptations, using stationary air bikes. Thirty-two recreationally active individuals were randomly assigned to the 3 performance groups, such as 10-5-SIT (n = 11), 20-10-SIT (n = 10), and MICT (n = 11), to train 3 days per week for 4 weeks. Moderate-intensity continuous training included 30 minutes of cycling at 75% of maximal heart rate reserve, whereas the SIT protocols consisted of 3 sets of 8 intervals at all-out intensity. The 10-5-SIT and 20-10-SIT were performed with 10-second work:5-second rest and 20-second work:10-second rest, with 2.5- and 5-minute recovery periods between sets, respectively. A ramp protocol was used before and after the intervention via cycle ergometer to assess aerobic performance. Time to exhaustion (TTE), absolute V̇o2max (A-V̇o2max), relative V̇o2max (R-V̇o2max), and metabolic equivalents (METs) were measured and analyzed with 2-way mixed factorial analyses of variance (ANOVAs). In addition, total work (TW) during 12 sessions were recorded and analyzed with 1-way ANOVA. Significant (p < 0.05) differences were found for TW (10-5-SIT: 907.3 ± 332.0, 20-10-SIT: 1230.0 ± 188.1, and MICT: 2263.0 ± 896.9 calories) between groups. A significant main effect of time was observed for 10-5-SIT, 20-10-SIT, and MICT (p < 0.05) in TTE (increased by 7.3, 8.7, and 8.2%), A-V̇o2max (increased by 13.0, 11.8, and 13.6%), R-V̇o2max (increased by 12.6, 12.1, and 14.8%), and METs (increased by 12.7, 12.3, and 14.9%), respectively. Despite less volume and duration, both SIT protocols induced cardiorespiratory adaptations similar to MICT. These findings suggest that performing SIT on a stationary air bike is valuable because of time-efficiency and cardiorespiratory adaptations.

Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the ß1 integrin-RhoA-formin axis.

Lymphangiogenesis is an essential physiological process but also a determining factor in vascular-related pathological conditions. Angiopoietin-2 (Ang2) plays an important role in lymphatic vascular development and function and its upregulation has been reported in several vascular-related diseases, including cancer. Given the established role of the small GTPase RhoA on cytoskeleton-dependent endothelial functions, we investigated the relationship between RhoA and Ang2-induced cellular activities. This study shows that Ang2-driven human dermal lymphatic endothelial cell migration depends on RhoA. We demonstrate that Ang2-induced migration is independent of the Tie receptors, but dependent on ß1 integrin-mediated RhoA activation with knockdown, pharmacological approaches, and protein sequencing experiments. Although the key proteins downstream of RhoA, Rho kinase (ROCK) and myosin light chain, were activated, blockade of ROCK did not abrogate the Ang2-driven migratory effect. However, formins, an alternative target of RhoA, were identified as key players, and especially FHOD1. The Ang2-RhoA relationship was explored in vivo, where lymphatic endothelial RhoA deficiency blocked Ang2-induced lymphangiogenesis, highlighting RhoA as an important target for anti-lymphangiogenic treatments.

Identification of a novel secreted metabolite cyclo(phenylalanyl-prolyl) from Batrachochytrium dendrobatidis and its effect on Galleria mellonella.

BACKGROUND: The fungus, Batrachochytrium dendrobatidis, is the causative agent of chytridiomycosis and a leading cause of global decline in amphibian populations. The first stages of chytridiomycosis include: inflammation, hyperkeratosis, lethargy, loss of righting reflex, and disruption of internal electrolyte levels leading to eventual death of the host. Previous work indicates that B. dendrobatidis can produce immunomodulatory compounds and other secreted molecules that regulate the growth of the fungus. In this study, filtrates of the fungus grown in media and water were subjected to ultra-performance liquid chromatography-mass spectrometry and analyzed using Compound Discoverer 3.0. RESULTS: Identification of cyclo(phenylalanyl-prolyl), chitobiose, and S-adenosylmethionine were verified by their retention times and fragmentation patterns from B. dendrobatidis supernatants. Previous studies have analyzed the effects of B. dendrobatidis on amphibian models, in vitro, or in cell culture. We studied the effects of live B. dendrobatidis cells, spent culture filtrates containing secreted metabolites, and cyclo(pheylalanyl-prolyl) on wax moth larvae (Galleria mellonella). Concentrated filtrates caused melanization within 24 h, while live B. dendrobatidis caused melanization within 48 h. CONCLUSIONS: Here we show B. dendrobatidis produces secreted metabolites previously unreported. The impacts of these chemicals were tested on an alternate non-amphibian model system that has been used for other fungi to study pathogenicity traits in this fungus.

Mattress Coil Spring Fatigue and Weight-Bearing Support: Comparison of Weight-Bearing and Non-Weight-Bearing Springs.

OBJECTIVE: The purpose of this study was to compare the firmness of used mattress coil springs from the areas bearing greatest body weight versus areas subjected to little compression. METHODS: Weight-bearing springs (WBS) extracted from the center of the mattresses (N = 32), and non-weight-bearing springs (NWBS) extracted from the head/foot were of the same mattresses. To determine spring weakness, a 1296-g ingot was placed on the coil, and the compression distance was measured (cm). In addition, a gauge was used to measure the amount of pressure required to compress the coil springs a distance of 2 cm. Comparison between WBS and NWBS data were statistically treated using independent t tests and a 1-way analysis of variance. RESULTS: There were no significant group differences in weight or height in unloaded coils. However, there were significant (P < .05) differences in coil spring compression distance under load (WBS = 2.78 ± 0.34 cm; NWBS = 1.52 ± 0.39 cm) and force gauge compression (WBS = 1090.51 ± 88.42 g; NWBS = 1213.12 ± 71.38 g) between groups. CONCLUSION: This study found that WBSs were weaker when compressed than the NWBS from used mattresses, and such characteristics may not be visually apparent in a mattress when not in use. Thus, coil springs in bedding systems may eventually fail to provide the initial structural support after use. Such sagging may compromise sleep posture with accompanying poor sleep quality and quantity.

Mouse model of Alzheimer's disease demonstrates differential effects of early disease pathology on various brain regions.

Different parts of the brain are affected distinctively in various stages of the Alzheimer's disease (AD) pathogenesis. Identifying the biochemical changes in specific brain regions is key to comprehend the neuropathological mechanisms in early pre-symptomatic phases of AD. Quantitative proteomics profiling of four distinct areas of the brain of young APP/PS1 mouse model of AD was performed followed by biochemical pathway enrichment analysis. Findings revealed fundamental compositional and functional shifts even in the early stages of the disease. This novel study highlights unique proteome and biochemical pathway alterations in specific regions of the brain that underlie the early stages of AD pathology and will provide a framework for future longitudinal studies. The proteomics data were deposited into the ProteomeXchange Consortium via PRIDE with the identifier PXD019192.

Similar Anaerobic and Aerobic Adaptations After 2 High-Intensity Interval Training Configurations: 10:5 s vs. 20:10 s Work-to-Rest Ratio.

ABSTRACT: Moghaddam, M, Estrada, CA, Muddle, TWD, Magrini, MA, Jenkins, NDM, and Jacobson, BH. Similar anaerobic and aerobic adaptations after 2 high-intensity interval training configurations: 10:5 s vs. 20:10 s work-to-rest ratio. J Strength Cond Res 35(6): 1685-1692, 2021-This study compares the effects of 2 high-intensity interval training (HIIT) configurations, a 10-5 vs. a 20-10 second work-to-rest ratio, on anaerobic and aerobic performance. Thirty-four individuals were randomly assigned to 10-5-HIIT (n = 17) and 20-10-HIIT (n = 17) groups to complete 6 cycles of 6 exercises, 3 days a week for 4 weeks. The 10-5-HIIT was performed with 10 s:5 s work-to-rest ratio with 1-minute recovery between cycles, while the 20-10-HIIT was performed with 20 s:10 s work-to-rest ratio followed by a 2-minute recovery. Anaerobic (i.e., peak power [PP], anaerobic capacity [AC], anaerobic power [AP], and total work [TW]) and aerobic fitness (i.e., time to exhaustion [TE], absolute V̇o2max [A-V̇o2max], relative V̇o2max [R-V̇o2max]) were measured with pre-training and post-training intervention. A significant main effect time was observed for both 10-5-HIIT and 20-10-HIIT (p < 0.05) in PP (9.2%, 5.7%); AC (14.9%, 8.6%); AP (9.0%, 6.2%); TW (15.1%, 8.5%); TE (4.3%, 5.5%); A-V̇o2max (9.4%, 8.9%); R-V̇o2max (8.5%, 8.2%), respectively. In conclusion, individuals may be able to achieve similar health benefits as 20-10-HIIT by performing 10-5-HIIT, despite exercising for 50% less total time. High-intensity interval training has been suggested as a "time-efficient" mode of exercise that can mitigate the most significant barrier to physical activity, "lack of time." Both 10-5-HIIT and 20-10-HIIT can induce performance adaptations to a similar extent. However, because of shorter time commitment, performing 10-5-HIIT at 10 s:5 s work-to-rest ratio may offer a shorter and equally efficient interval. Functional fitness training during HIIT protocols seems to be as beneficial as ergometer-based HIIT to improve anaerobic and aerobic performance.

Recent Advances of Functional Proteomics in Gastrointestinal Cancers- a Path towards the Identification of Candidate Diagnostic, Prognostic, and Therapeutic Molecular Biomarkers.

Gastrointestinal (GI) cancer remains one of the common causes of morbidity and mortality. A high number of cases are diagnosed at an advanced stage, leading to a poor survival rate. This is primarily attributed to the lack of reliable diagnostic biomarkers and limited treatment options. Therefore, more sensitive, specific biomarkers and curative treatments are desirable. Functional proteomics as a research area in the proteomic field aims to elucidate the biological function of unknown proteins and unravel the cellular mechanisms at the molecular level. Phosphoproteomic and glycoproteomic studies have emerged as two efficient functional proteomics approaches used to identify diagnostic biomarkers, therapeutic targets, the molecular basis of disease and mechanisms underlying drug resistance in GI cancers. In this review, we present an overview on how functional proteomics may contribute to the understanding of GI cancers, namely colorectal, gastric, hepatocellular carcinoma and pancreatic cancers. Moreover, we have summarized recent methodological developments in phosphoproteomics and glycoproteomics for GI cancer studies.

Prediction of HCV load using genotype, liver biomarkers, and clinical symptoms by a mathematical model in patients with HCV infection.

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross-sectional study, blood samples were taken from 249 recently diagnosed HCV-infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV-RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut-off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV-RNA load. Regression model: log viral load = 7.69 - 1.01 × G3 - 0.7 × G1 + 0.002 × ALT - 0.86 × fatigue.

Global Positioning System Monitoring of Selected Physical Demands of NCAA Division I Football Players During Games.

Bayliff, GE, Jacobson, BH, Moghaddam, M, and Estrada, C. Global positioning system monitoring of selected physical demands of NCAA Division I football players during games. J Strength Cond Res 33(5): 1185-1191, 2019-Global positioning system (GPS) tracking of athletes in selected sports is a new innovation into obtaining comprehensive data regarding physical output with respect to distance travelled (DT), acceleration, and change of direction. The purpose of this study was to determine selected physical demands of American football players during the course of games and to compare such data by player position. Offensive lineman (OL) (n = 14) and defensive lineman (DL) (n = 9) and offensive wide receivers (WRs) (n = 10) and defensive backs (DBs) (n = 10) were fitted with GPS monitors during games. Collected data included DT, maximum velocity (MV), and acceleration (AC), deceleration (DC) distance at 2 intensities. Results indicated that DBs travelled significantly (p < 0.05) greater distances than OL and WR, but not DL. For MV, DBs and WRs were not significantly different but were significantly different from OL and DL. Also, DL was significantly different than OL. For the most intense acceleration (3-10 m·s), WR accelerated significantly further than all other positions and DBs accelerated further than DL and OL. There was not significant difference between DL and OL. For deceleration at the high-intensity measure, significant differences existed among all positions. Underestimation of workload during games could be a factor for the overuse and soft-tissue injuries and more serious injuries. Furthermore, using GPS tracking of similar variables as found in this study may benefit coaches and trainers in many other high-intensity sports.

Higher prevalence of water pipe compared to cigarette smoking among medical students in Southeast Iran.

OBJECTIVES: Smoking of water pipe (WP) and cigarettes has recently turned into a major global health burden. The present study aimed at assessing WP and cigarette smoking among Zahedan University of Medical Sciences (ZUMS) students in Iran. METHODS: A cross-sectional survey was conducted on 500 students in ZUMS (182 males, 318 females). The subjects were selected through randomized cluster sampling. Morgan's chart was applied to calculate the sample size; 96.6% of the attendees completed a questionnaire designed to address the aims of the study. RESULTS: The mean age of the subjects was 21.2 ± 2.4 years. WP and cigarette smoker rates were at 31.2% and 15.2%, respectively. The age of smoking initiation ranged between 15 and 20 years. Friends played crucial roles in triggering the smoking in both groups of WP and cigarette smokers (78% and 54%, respectively). The main reasons for WP and cigarette smoking were entertainment followed by curiosity. Furthermore, males used more cigarette (26.5 vs. 8.7%) and WP (50.6 vs. 20.4%) than females. Among father and mother smokers, respectively, 54.2% and 60% of children were also WP smokers (p = 0.001). Also, 21.9% and 60% of children smoking cigarettes had father and mother smokers, respectively (p = 0.05). CONCLUSION: Tobacco use, especially for WP seems to be at alarming rates among medical students in Iran. It is highly recommended to control the progressive prevalence of WP smoking by governmental/academic preventive measures as educational and smoking cessation activities.

Association of socioeconomic risk factors with under 5-year mortality in Zabol, Iran, during 2011-2015.

Background: Under-5 mortality is an important health indicator of a country's development and every country is committed todecrease it. Children under-5 years are vulnerable to the imbalance of socioeconomic inequality and are dependent on the adults toremain healthy. The aim of this study was to determine the association of socioeconomic factors with under-5 mortality in Zabol. Methods: This descriptive cross sectional study was performed on 2001 children younger than 5 years who were under the coverageof Zabol University of Medical Sciences between 2011 and 2015. The data were collected using standard questionnaires on mortality ofinfant and children 1-59 months old, questionnaires determining socioeconomic condition, and health center data files. The analyseswere performed using SPSS software version 21, and significance level was set at 0.05 for all tests. Results: The most common causes of death under 5 years of age included immaturity, congenital defects, and respiratory diseases. Inthe logistic regression model, father's addiction, maternal literacy, socioeconomic level, and household family size were significantlyassociated with under-5 mortality (P<0.05). Moreover, there was a correlation between a congenital defect in the Zahak region andimmaturity in the Hamun region with under-5 mortality. Conclusion: Low socioeconomic status, parental addiction, and low education level were the most probable risk factors for under 5mortality.

Recent advances in mass spectrometric analysis of glycoproteins.

Glycosylation is one of the most common posttranslational modifications of proteins that plays essential roles in various biological processes, including protein folding, host-pathogen interaction, immune response, and inflammation and aberrant protein glycosylation is a well-known event in various disease states including cancer. As a result, it is critical to develop rapid and sensitive methods for the analysis of abnormal glycoproteins associated with diseases. Mass spectrometry (MS) in conjunction with different separation methods, such as capillary electrophoresis (CE), ion mobility (IM), and high performance liquid chromatography (HPLC) has become a popular tool for glycoprotein analysis, providing highly informative fragments for structural identification of glycoproteins. This review provides an overview of the developments and accomplishments in the field of glycomics and glycoproteomics reported between 2014 and 2016.

Nanospray liquid chromatography/tandem mass spectrometry analysis of steroids from gray whale blubber.

RATIONALE: Analysis of steroids from precious blubber biopsies obtained from marine mammals, especially endangered species, can provide valuable information on their endocrine status. Challenges with currently used ELISA methodology include lack of absolute quantitation and incompatibility with multiple steroids analysis due to limited biopsy mass. Development of a sensitive, accurate analytical method for this purpose is critical. METHODS: A nanospray liquid chromatography/tandem mass spectrometry (nanoLC/MS/MS) method was validated for sensitive, specific and quantitative analysis of three steroid hormones, without derivatization, extracted from 50 mg blubber samples. Data was acquired with an LTQ XL ion trap mass spectrometer in positive ion mode, using single reaction monitoring. All three steroids were analyzed in a single run. Cholic acid was used as a surrogate internal standard for quantitation due to its steroidal structure and lack of measurable endogenous levels in blubber. RESULTS: The lowest limits of quantitation for progesterone, testosterone, and hydrocortisone were significantly improved compared to previous studies using conventional LC/MS/MS. The lowest limit of detection was 7 fg/µL using a 1 µL injection volume. Calibration curves for steroid quantification showed good linearity (r2 >0.99) between 14 and 3620 fg/µL, and accuracy was <20% for interday and <10% for intraday. After validation, the method was successfully applied to quantification of steroids in gray whale blubber samples. CONCLUSIONS: The nanoLC/MS/MS method is more sensitive than traditional LC/MS/MS for steroid analysis. It is also compatible with other important biopsy analyses due to its small blubber mass requirement. This will benefit the reproductive and stress assessments for all marine mammals, particularly endangered populations. Copyright © 2017 John Wiley & Sons, Ltd.

Grain size-dependent crystal plasticity constitutive model for polycrystal materials.

Consideration of a core and mantle configuration for individual grains is a prominent method to capture the grain size-dependence in the constitutive models for polycrystal material. The mantle represents a region of the grain volume near the grain boundary where mechanical deformation is influenced by the grain boundaries, while the core represents the inner region of the grain volume. The grain size-dependence is then realized by assigning a set of values for the mechanical properties in the mantle that are different from those of the core region. However, these values for the mechanical properties of the mantle region are typically chosen arbitrarily, guided solely by the quality of the agreement between a model's predicted stress-strain behavior with that obtained experimentally. In the present study, a physics-based method to develop the grain size-dependent crystal plasticity constitutive model on the core and mantle configuration for polycrystal materials is presented. The method is based on the assumption that any resistance to dislocation nucleation and motion in a material manifests as an increase in yield strength and a decrease in strain-hardening modulus, and the mutual relationship between yield strength and strain-hardening is an inherent material property that determines the plasticity of that specific material. Accordingly, the same single crystal plasticity constitutive model that describes the behavior of the material under loading can be used to capture the increased resistance to dislocation nucleation and motion in the grain boundary influence region. The physics-based modeling is facilitated by introducing a shear flow strain distribution in the phenomenological formulation and a pile-up of dislocation density distribution in the dislocation based formulation, such that, the resulting variations in the yield strength and the strain-hardening modulus are identical to that produced by the increased resistance in the grain boundary influence region. Thus, the increase in strength and the decrease in the strain-hardening modulus, determined as spatially varying local material properties in the mantle, are mutually related through the grain size-independent inherent plastic properties specific to the material. A simplified model that considers the grain boundary effect averaged over the grain volume is also developed under this general framework. Implementation of this simplified model is demonstrated by considering the case of a power law flow rule and a hyperbolic-secant hardening rule for the phenomenological formulation, and Taylor strength relation for the dislocation based formulation. Finally, the grain size-dependent constitutive model is validated by comparing the predicted stress-strain behavior of polycrystal copper samples under uniaxial loading with experimental results.

Synthesis of d-labeled and unlabeled ethyl succinic anhydrides and application to quantitative analysis of peptides by isotope differential mass spectrometry.

Ethyl succinic anhydride and its d5-labeled version have been synthesized and applied to quantitative analysis of peptides in combination with MALDI or ESI mass spectrometry. These modifiers react with amino groups in the N-termini and lysine side chains in proteins, and therefore the combination of these modifiers was shown to be a useful tool for quantification of peptides and hence for proteomics research.

Reduced Serum Levels of Zinc and Superoxide Dismutase in Obese Individuals.

The oxidant-stress (OS) has an essential role to play in the pathogenesis and progression of many diseases. OS is the outcome when the level of free-radical-formation is increased or protective-antioxidant-mechanisms are compromised. Its value is expected to increase, although its emerging roles have not been conclusive in different studies. The objective of this study was to explore the level of zinc, copper, and antioxidant in response to obesity-related-stress by measuring superoxide-dismutase (SOD) levels as a key antioxidant-enzyme in 706 individuals with/without obesity. Anthropometric/biochemical parameters including total-cholesterol (TC), fasting-blood-glucose, high-density-lipoprotein (HDL), low-density-lipoprotein, and triglycerides were determined. The activity of SOD was measured followed by the measurement of Cu and Zn levels. Obese subjects had a significantly higher level of body mass index (BMI) and TC, while the level of HDL was lower in the obese group, as compared to the related values in control subjects. The level of Zn was significantly decreased in the obese group, while the level of Cu and Cu/Zn ratio increased. Additionally, we observed that the SOD level was less in obese subjects when compared to that in the non-obese subjects. In addition to the complications of high BMI, low level of Zn and SOD in obesity can be considered a risk factor, resulting in a reduced antioxidant response, supporting the need for identifying a suitable treatment option for this group.

A loop unique to ferredoxin-dependent glutamate synthases is not absolutely essential for ferredoxin-dependent catalytic activity.

It had been proposed that a loop, typically containing 26 or 27 amino acids, which is only present in monomeric, ferredoxin-dependent, "plant-type" glutamate synthases and is absent from the catalytic α-subunits of both NADPH-dependent, heterodimeric glutamate synthases found in non-photosynthetic bacteria and NADH-dependent heterodimeric cyanobacterial glutamate synthases, plays a key role in productive binding of ferredoxin to the plant-type enzymes. Site-directed mutagenesis has been used to delete the entire 27 amino acid-long loop in the ferredoxin-dependent glutamate synthase from the cyanobacterium Synechocystis sp. PCC 6803. The specific activity of the resulting loopless variant of this glutamate synthase, when reduced ferredoxin serves as the electron donor, is actually higher than that of the wild-type enzyme, suggesting that this loop is not absolutely essential for efficient electron transfer from reduced ferredoxin to the enzyme. These results are consistent with the results of an in-silico study that suggests that the loop is unlikely to interact directly with ferredoxin in the energetically most favorable model of a 1:1 complex of ferredoxin with the wild-type enzyme.

Effects of the flavanone combination hesperetin-naringenin, and orange and grapefruit juices, on airway inflammation and remodeling in a murine asthma model.

We investigated whether flavanones, hesperetin-naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non-asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra-alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM-induced asthma.