Futile cycles: Emerging utility from apparent futility.

Futile cycles are biological phenomena where two opposing biochemical reactions run simultaneously, resulting in a net energy loss without appreciable productivity. Such a state was presumed to be a biological aberration and thus deemed an energy-wasting "futile" cycle. However, multiple pieces of evidence suggest that biological utilities emerge from futile cycles. A few established functions of futile cycles are to control metabolic sensitivity, modulate energy homeostasis, and drive adaptive thermogenesis. Yet, the physiological regulation, implication, and pathological relevance of most futile cycles remain poorly studied. In this review, we highlight the abundance and versatility of futile cycles and propose a classification scheme. We further discuss the energetic implications of various futile cycles and their impact on basal metabolic rate, their bona fide and tentative pathophysiological implications, and putative drug interactions.

The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: an analysis of the data from Toxicity Reference Database (ToxRefDB).

Absolute (ALW) and relative (RLW) liver weight changes are sensitive endpoints in repeat-dose rodent toxicity studies, and their changes are often used for quantitative assessment of health effects induced by hepatotoxic chemicals using the benchmark dose-response modeling (BMD) approach. To find biologically relevant liver weight changes to chemical exposures, we evaluated all data available for liver weight changes and associated liver histopathologic findings from the Toxicity Reference Database (ToxRefDB). Our analysis of 389 subchronic mouse and rat studies for 273 chemicals found significant differences in treatment-related ALW and RLW changes between dose groups with and without liver histopathologic changes. In addition, we demonstrate that chemical treatment-induced ALW and RLW changes can predict the presence of histopathologic findings and inform the selection of biologically relevant liver weight changes for BMD modeling and derivation of toxicity values.

Long-term fasting induced basal thermogenesis flexibility in female Japanese quails.

Male Japanese quails (Coturnix japonica) have been found to exhibit a three-phase metabolic change when subjected to prolonged fasting, during which basal thermogenesis is significantly reduced. A study had shown that there is a significant difference in the body temperature between male and female Japanese quails. However, whether female Japanese quails also show the same characteristic three-phase metabolic change during prolonged fasting and the underlying thermogenesis mechanisms associated with such changes are still unclear. In this study, female Japanese quails were subjected to prolonged starvation, and the body mass, basal metabolic rate (BMR), body temperature, mass of tissues and organs, body fat content, the state-4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the muscle and liver of these birds were measured to determine the status of metabolic changes triggered by the starvation. In addition, the levels of glucose, triglyceride (TG) and uric acid, and thyroid hormones (T3 and T4) in the serum and the mRNA levels of myostatin (MSTN) and avian uncoupling protein (av-UCP) in the muscle were also measured. The results revealed the existence of a three-phase stage similar to that found in male Japanese quails undergoing prolonged starvation. Fasting resulted in significantly lower body mass, BMR, body temperature, tissues masses and most organs masses, as well as S4R and CCO activity in the muscle and liver. The mRNA level of av-UCP decreased during fasting, while that of MSTN increased but only during Phase I and II and decreased significantly during Phase III. Fasting also significantly lowered the T3 level and the ratio of T3/T4 in the serum. These results indicated that female Japanese quails showed an adaptive response in basal thermogenesis at multiple hierarchical levels, from organismal to biochemical, enzyme and cellular level, gene and endocrine levels and this integrated adjustment could be a part of the adaptation used by female quails to survive long-term fasting.

Effect of Fungicide Application and Corn Hybrid Class on the Presence of Fusarium graminearum and the Concentration of Deoxynivalenol in Ear and Stalk Parts of Corn (Zea mays) Used for Silage.

In Wisconsin, the use of brown midrib (BMR) corn (Zea mays) hybrids for ensiling and subsequent feeding to dairy cows is quite common. The overall milk production from cows fed silage from BMR hybrids is typically higher than those fed silage made from dual-purpose hybrids. Gibberella diseases (ear and stalk rot) caused by Gibberella zeae (anamorph; Fusarium graminearum) and the accompanying accumulation of the mycotoxin deoxynivalenol (DON) can be significant issues during the field production of BMR hybrids. The work presented here aimed to understand the role of hybrid class on the distribution of F. graminearum DNA and DON in the ear and stalk parts of corn for silage. An ear and stalk partitioned sample experiment was conducted on silage corn from field trials in Arlington, Wisconsin, in 2020 and 2021. The trials were arranged in a randomized complete block design in both years, including one BMR hybrid, one dual-purpose hybrid, and seven fungicide application regimes. Paired ear and stalk samples were physically separated, dried, and ground at harvest before determining the concentration of F. graminearum DNA and DON in each sample. Across both years, the main effects of hybrid, treatment, and plant part were not significant (P > 0.1) on DON concentration. However, the hybrid-by-plant part interaction effect was significant (P < 0.01). Ears of the BMR hybrid accumulated the most DON, whereas the dual-purpose hybrid ears had the lowest DON concentration. The concentrations of DON and F. graminearum DNA were significantly (P < 0.01) and highly correlated in the ear (r = 0.73) but not in the stalk (r = 0.09, P = 0.33). These findings suggest that DON accumulation in the corn ear is a major contributor in the difference observed in the total DON between the hybrid classes. Therefore, growers and researchers are encouraged to focus production and breeding on hybrids in both classes that accumulate less DON in ears, resulting in lower total DON in corn chopped for silage.

Trends in measuring BMR and RMR after spinal cord injury: a comprehensive review.

Studying factors that contribute to our understanding of maintaining normal energy balance are of paramount significance following spinal cord injury (SCI). Accurate determination of energy needs is crucial for providing nutritional guidance and managing the increasing prevalence of malnutrition or obesity after SCI. BMR represents 75-80 % of the total energy expenditure in persons with SCI. Accurately measuring BMR is an important component for calculating total energetic needs in this population. Indirect calorimetry is considered the gold-standard technique for measuring BMR. However, technical challenges may limit its applications in large cohort studies and alternatively rely on prediction equations. Previous work has shown that BMR changes in response to disuse and exercise in the range of 15-120 %. Factors including sex, level of injury and type of assistive devices may influence BMR after SCI. RMR is erroneously used interchangeably for BMR, which may result in overestimation of energetic intake when developing nutritional plans. To address this concern, we comprehensively reviewed studies that conducted BMR (n=15) and RMR (n=22) in persons with SCI. The results indicated that RMR is 9 % greater than BMR in persons with SCI. Furthermore, the SCI-specific prediction equations that incorporated measures of fat-free mass appeared to accurately predict BMR. Overall, the current findings highlighted the significance of measuring BMR as well as encouraging the research and clinical community to effectively establish countermeasures to combat obesity after SCI.

Basement membrane-related regulators for prediction of prognoses and responses to diverse therapies in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a global health threat. Finding a novel biomarker for assessing the prognosis and new therapeutic targets is vital to treating this patient population. Our study aimed to explore the contribution of basement membrane-related regulators (BMR) to prognostic assessment and therapeutic response prediction in HCC. MATERIAL AND METHODS: The RNA sequencing and clinical information of HCC were downloaded from TCGA-LIHC, ICGC-JP, GSE14520, GSE104580, and CCLE datasets. The BMR signature was created by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and used to separate HCC patients into low- and high-risk groups. We conducted analyses using various R 4.1.3 software packages to compare prognoses and responses to immunotherapy, transcatheter arterial chemoembolization (TACE), and chemotherapeutic drugs between the groups. Additionally, stemness indices, molecular functions, and somatic mutation analyses were further explored in these subgroups. RESULTS: The BMR signature included 3 basement membrane-related genes (CTSA, P3H1, and ADAM9). We revealed that BMR signature was an independent risk contributor to poor prognosis in HCC, and high-risk group patients presented shorter overall survival. We discovered that patients in the high-risk group might be responsive to immunotherapy, while patients in the low-risk group may be susceptible to TACE therapy. Over 300 agents were screened to identify effective drugs for the two subgroups. CONCLUSION: Overall, basement membrane-related regulators represent novel biomarkers in HCC for assessing prognosis, response to immunotherapy, the effectiveness of TACE therapy, and drug susceptibility.

Revised Harris-Benedict Equation: New Human Resting Metabolic Rate Equation.

This paper contains a revision of the Harris-Benedict equations through the development and validation of new equations for the estimation of resting metabolic rate (RMR) in normal, overweight, and obese adult subjects, taking into account the same anthropometric parameters. A total of 722 adult Caucasian subjects were enrolled in this analysis. After taking a detailed medical history, the study enrolled non-hospitalized subjects with medically and nutritionally controlled diseases such as diabetes mellitus, cardiovascular disease, and thyroid disease, excluding subjects with active infections and pregnant or lactating women. Measurement of somatometric characteristics and indirect calorimetry were performed. The values obtained from RMR measurement were compared with the values of the new equations and the Harris-Benedict, Mifflin-St Jeor, FAO/WHO/UNU, and Owen equations. New predictive RMR equations were developed using age, body weight, height, and sex parameters. RMR males: (9.65 × weight in kg) + (573 × height in m) - (5.08 × age in years) + 260; RMR females: (7.38 × weight in kg) + (607 × height in m) - (2.31 × age in years) + 43; RMR males: (4.38 × weight in pounds) + (14.55 × height in inches) - (5.08 × age in years) + 260; RMR females: (3.35 × weight in pounds) + (15.42 × height in inches) - (2.31 × age in years) + 43. The accuracy of the new equations was tested in the test group in both groups, in accordance with the resting metabolic rate measurements. The new equations showed more accurate results than the other equations, with the equation for men (R-squared: 0.95) showing better prediction than the equation for women (R-squared: 0.86). The new equations showed good accuracy at both group and individual levels, and better reliability compared to other equations using the same anthropometric variables as predictors of RMR. The new equations were created under modern obesogenic conditions, and do not exclude individuals with regulated (dietary or pharmacological) Westernized diseases (e.g., cardiovascular disease, diabetes, and thyroid disease).

Impact of the "Zero Resistance" program on acquisition of multidrug-resistant bacteria in patients admitted to Intensive Care Units in Spain. A prospective, intervention, multimodal, multicenter study.

OBJECTIVE: To assess the impact of a multimodal interventional project ("Zero Resistance") on the acquisition of multidrug-resistant bacteria (MDR-B) during the patient's ICU stay. DESIGN: Prospective, open-label, interventional, multicenter study. SETTING: 103 ICUs. PATIENTS: Critically ill patients admitted to the ICUs over a 27-month period. INTERVENTIONS: Implementation of a bundle of 10 recommendations to prevent emergence and spread of MDR-B in the ICU. MAIN VARIABLE OF INTEREST: Rate of patients acquiring MDR-B during their ICU stay, with differentiation between colonization and infection. RESULTS: A total of 139,505 patients were included. In 5409 (3.9%) patients, 6020 MDR-B on ICU admission were identified, and in 3648 (2.6%) patients, 4269 new MDR-B during ICU stay were isolated. The rate of patients with MDR-B detected on admission increased significantly (IRR 1.43, 95% CI 1.31-1.56) (p<0.001) during the study period, with an increase of 32.2% between the initial and final monthly rates. On the contrary, the rate of patients with MDR-B during ICU stay decreased non-significantly (IRR 0.93, 95% CI 0.83-1.03) (p=0.174), with a 24.9% decrease between initial and final monthly rates. According to the classification into colonization or infection, there was a highly significant increase of MDR-B colonizations detected on admission (IRR 1.69, 95% CI 1.52-1.83; p<0.0001) and a very significant decrease of MDR-B-infections during ICU stay (IRR 0.67, 95% CI 0.57-0.80, p<0.0001). CONCLUSIONS: The implementation of ZR project-recommendations was associated with a significantly reduction an infection produced by MDR-B acquired during the patient's ICU stay.

Molecular Lego of Human Cytochrome P450: The Key Role of Heme Domain Flexibility for the Activity of the Chimeric Proteins.

The cytochrome P450 superfamily are heme-thiolate enzymes able to carry out monooxygenase reactions. Several studies have demonstrated the feasibility of using a soluble bacterial reductase from Bacillus megaterium, BMR, as an artificial electron transfer partner fused to the human P450 domain in a single polypeptide chain in an approach known as 'molecular Lego'. The 3A4-BMR chimera has been deeply characterized biochemically for its activity, coupling efficiency, and flexibility by many different biophysical techniques leading to the conclusion that an extension of five glycines in the loop that connects the two domains improves all the catalytic parameters due to improved flexibility of the system. In this work, we extend the characterization of 3A4-BMR chimeras using differential scanning calorimetry to evaluate stabilizing role of BMR. We apply the 'molecular Lego' approach also to CYP19A1 (aromatase) and the data show that the activity of the chimeras is very low (<0.003 min−1) for all the constructs tested with a different linker loop length: ARO-BMR, ARO-BMR-3GLY, and ARO-BMR-5GLY. Nevertheless, the fusion to BMR shows a remarkable effect on thermal stability studied by differential scanning calorimetry as indicated by the increase in Tonset by 10 °C and the presence of a cooperative unfolding process driven by the BMR protein domain. Previously characterized 3A4-BMR constructs show the same behavior of ARO-BMR constructs in terms of thermal stabilization but a higher activity as a function of the loop length. A comparison of the ARO-BMR system to 3A4-BMR indicates that the design of each P450-BMR chimera should be carefully evaluated not only in terms of electron transfer, but also for the biophysical constraints that cannot always be overcome by chimerization.

The seasonal variation of basal metabolic rate is related to the expression of torpor among small mammals.

A variety of responses to climate seasonality have evolved by small mammals, including adjustments of the basal rate of metabolism (BMR) and the use of daily or seasonal torpor (here referred to as short-bout and long-bout torpor). The seasonal variation of their BMR is known to depend mainly on the concurrent variation of body mass, but it should also be affected by structural and functional changes occurring within the body that could depend on the expression of torpor. Thus it was hypothesized that BMR seasonality is related to the expression of torpor at an interspecific level. Seasonal BMR and body mass data were gathered from the literature and phylogenetic comparative analyses were done to test this hypothesis among mammals of less than 1 kg. BMR seasonality (dBMR) was quantified as the log-transformed ratio of the mean whole-animal BMR reported for the period P2 (autumn-winter) over that for the period P1 (spring-summer). Predictors were the seasonal body mass adjustment (dm), mean body mass (m) and torpor expression (TO, a three-level factor: no torpor, short-bout torpor, long-bout torpor). The seasonal variation of BMR was significantly related to dm but also to TO. Accounting for dm, species expressing long-bout torpor, but not those entering short-bout torpor, collectively exhibited a lower dBMR than species not entering torpor. Fat storage and use by species entering long-bout torpor, alone, could not explain their lower dBMR, as the TO:dm interaction was not significant. The low dBMR of species entering long-bout torpor may result from their collective tendency to down-regulate more strongly costly visceral organs during P2. The dBMR of the different TO categories overlapped appreciably, which highlights our still limited knowledge of the BMR seasonality among small mammals.

Generation of human scFv-IgG1Fc antibodies for detection of lymphatic filarial recombinant antigens, BmR1 and BmSXP.

Lymphatic filariasis is a neglected parasitic disease that affects millions in tropical and subtropical countries and is caused by Wuchereria and Brugia species. Specific and sensitive detection methods are essential in mapping infected areas where rapid tests are needed to cover underdeveloped and remote regions, which facilitates eliminating the disease as a public health problem. A few commercialized rapid tests based on antigen or antibody detection are available, but the former only detects infection by Wuchereria species and cross-reacts with nonlymphatic filaria, whereas antibody detection might provide positive results of previous infection. Here, we report the production of three different recombinant immunoglobulin gamma (IgG)1 antibodies based on scFvs previously generated via human antibody phage display technology, that is, anti-BmR1 clone 4, anti-BmXSP clone 5B, and anti-BmXSP clone 2H2. The scFv sequences were cloned into a pCMV-IgG1 vector, then transfected into a HEK293F cell line. The generated antibodies were found to be able to bind to their respective targets even at relatively low concentration. Conjugation of Fc to scFv induces binder stability and provides multiple labeling sites for probes and signaling molecules that can be used in rapid tests.

Babesia microti Immunoreactive Rhoptry-Associated Protein-1 Paralogs Are Ancestral Members of the Piroplasmid-Confined RAP-1 Family.

Babesia, Cytauxzoon and Theileria are tick-borne apicomplexan parasites of the order Piroplasmida, responsible for diseases in humans and animals. Members of the piroplasmid rhoptry-associated protein-1 (pRAP-1) family have a signature cysteine-rich domain and are important for parasite development. We propose that the closely linked B. microti genes annotated as BMR1_03g00947 and BMR1_03g00960 encode two paralogue pRAP-1-like proteins named BmIPA48 and Bm960. The two genes are tandemly arranged head to tail, highly expressed in blood stage parasites, syntenic to rap-1 genes of other piroplasmids, and share large portions of an almost identical ~225 bp sequence located in their 5' putative regulatory regions. BmIPA48 and Bm960 proteins contain a N-terminal signal peptide, share very low sequence identity (<13%) with pRAP-1 from other species, and harbor one or more transmembrane domains. Diversification of the piroplasmid-confined prap-1 family is characterized by amplification of genes, protein domains, and a high sequence polymorphism. This suggests a functional involvement of pRAP-1 at the parasite-host interface, possibly in parasite adhesion, attachment, and/or evasion of the host immune defenses. Both BmIPA48 and Bm960 are recognized by antibodies in sera from humans infected with B. microti and might be promising candidates for developing novel serodiagnosis and vaccines.

Pathogen and drought stress affect cell wall and phytohormone signaling to shape host responses in a sorghum COMT bmr12 mutant.

BACKGROUND: As effects of global climate change intensify, the interaction of biotic and abiotic stresses increasingly threatens current agricultural practices. The secondary cell wall is a vanguard of resistance to these stresses. Fusarium thapsinum (Fusarium stalk rot) and Macrophomina phaseolina (charcoal rot) cause internal damage to the stalks of the drought tolerant C4 grass, sorghum (Sorghum bicolor (L.) Moench), resulting in reduced transpiration, reduced photosynthesis, and increased lodging, severely reducing yields. Drought can magnify these losses. Two null alleles in monolignol biosynthesis of sorghum (brown midrib 6-ref, bmr6-ref; cinnamyl alcohol dehydrogenase, CAD; and bmr12-ref; caffeic acid O-methyltransferase, COMT) were used to investigate the interaction of water limitation with F. thapsinum or M. phaseolina infection. RESULTS: The bmr12 plants inoculated with either of these pathogens had increased levels of salicylic acid (SA) and jasmonic acid (JA) across both watering conditions and significantly reduced lesion sizes under water limitation compared to adequate watering, which suggested that drought may prime induction of pathogen resistance. RNA-Seq analysis revealed coexpressed genes associated with pathogen infection. The defense response included phytohormone signal transduction pathways, primary and secondary cell wall biosynthetic genes, and genes encoding components of the spliceosome and proteasome. CONCLUSION: Alterations in the composition of the secondary cell wall affect immunity by influencing phenolic composition and phytohormone signaling, leading to the action of defense pathways. Some of these pathways appear to be activated or enhanced by drought. Secondary metabolite biosynthesis and modification in SA and JA signal transduction may be involved in priming a stronger defense response in water-limited bmr12 plants.

Determination of benchmark doses for linear furanocoumarin consumption associated with inhibition of cytochrome P450 1A2 isoenzyme activity in healthy human adults.

Millions of individuals globally consume traditional herbal medicines (THMs), which contain abundant amounts of linear furanocoumarins. Linear furanocoumarins (i.e., 8-methoxypsoralen, 5-methoxypsoralen, and isopimpinellin) are inhibitors of cytochrome P450 (CYP) isoenzymes including 1A2, a major enzyme involved in drug metabolism and carcinogen bioactivation. Despite the high consumption of furanocoumarin-containing THMs, no studies have measured the furanocoumarin consumption level that triggers an inhibition to CYP1A2 activity in humans. The first objective was to verify if the potencies of the three furanocoumarins are additive towards the inhibition of CYP1A2 activity in vitro using concentration-addition and whole-mixture chemical-mixture-assessment models. A second objective was to determine the benchmark dose (BMD) with the mixtures of furanocoumarin oral doses, expressed as 8-MOP equivalents, and to assess the in vivo CYP1A2 activity, expressed as inhibition percentages. The in vitro results indicated that the three furanocoumarin inhibitory potencies were additive in the THM extracts, validating the use of the concentration-addition model in total furanocoumarin dose-equivalent calculations. Using the USEPA BMD software, the BMD was 18.9 µg 8-MOP equivalent/kg body weight. This information is crucial for furanocoumarin-related health-assessment studies and the regulation of THMs. Further studies should be performed for the remaining major metabolic enzymes to complete the safety profile of furanocoumarin-containing THMs and to provide accurate warning labelling.

Basal metabolic rate in free-ranging tropical birds lacks long-term repeatability and is influenced by ambient temperature.

Tropical birds live longer, have smaller clutches and invest more resources into self-maintenance than temperate species. These "slow" life-histories in tropical birds are accompanied by low basal metabolic rate (BMR). It has recently been suggested that the low BMR of tropical species may be related not to their slow "pace of life" or high ambient temperatures (Ta ) in tropical latitudes, but to the stability of environmental conditions in tropics. Since the repeatability of metabolic traits is higher in stable environments, such as laboratory conditions, we predicted that long-term repeatability of BMR in a tropical climate should be higher than in a temperate one. Contrary to our predictions, the repeatability of mass-independent BMR in 64 individuals of free-living tropical birds from Vietnam was low and insignificant after the species affiliation was taken into account. It indicates that BMR cannot be used as an individual long-term characteristic of tropical birds. On the other hand, tropical birds showed consistent differences in their mass-independent BMR at the interspecific level. Using BMR measurements from 1543 individuals of 134 species, we also found that different characteristics of Ta within the week preceding BMR measurements had a significant impact on the mass-independent BMR of tropical birds. The most significant effect was the difference between the absolute maximum and minimum Ta within a single week. Our results indicate that the physiology of tropical birds is more subject to changes than would be expected based on the notion of the stability of climatic conditions in the tropics.

Energetics of whiskered bats in comparison to other bats of the family Vespertilionidae.

Bats inhabit a variety of climate types, ranging from tropical to temperate zones, and environmental differences may therefore affect the basal metabolic rate (BMR) of bats from different populations. In the present study, we provide novel data on the energetics of whiskered bats (Myotis mystacinus), which is the smallest species within Chiroptera measured to date. We investigated the thermoregulatory strategies of M. mystacinus close to the northern limits of this species' distribution range and compared these data to other vespertilionid bats living in different climates. As mammals living in colder areas experience elevated thermoregulatory costs, often leading to an increase in BMR, we hypothesised that BMR of this northern population of whiskered bats would be higher than that of bats from climates with warm environmental temperatures. From a systematic literature search we obtained BMR estimates (N=47) from 24 species within Vespertilionidae. Our metabolic measurements of M. mystacinus in Norway (body mass of 4.4 g; BMR of 1.48 ml O2 g-1 h-1) were not different from other vespertilionid bats, based on the allometric equation obtained from the systematic literature search. Further, there was no effect of environmental temperature on BMR within Vespertilionidae. How these tiny bats adapt metabolically to high latitude living is thus still an open question. Bats do have a suite of physiological strategies used to cope with the varying climates which they inhabit, and one possible factor could be that instead of adjusting BMR they could express more torpor. This article has an associated First Person interview with the first author of the paper.

GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated.

BACKGROUND: Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect. METHODS: We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR). RESULTS: There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60. CONCLUSION: The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation. TRIAL REGISTRATION: The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.

Sorghum as Biofuel Crop: Interdisciplinary Methods to Enhance Productivity (Botany, Genetics, Breeding, Seed Technology, and Bioengineering).

Sorghum is a versatile crop cultivated since time immemorial. It fulfills the basic needs of mankind in the contest of food, feed, fodder, nutrition, and pharmaceutical uses. Now it adds one more paramount importance as a second-generation biofuel. It offers ethanol from grain, stem (sweet sorghum), and biomass (lignocellulose), and the previous one is discouraging because of food versus fuel conflict. However sorghum lignocellulosic biofuel are gaining momentum in order to conserve nature from depleting first-generation fuel. This chapter describes interdisciplinary approaches/methods involving understanding the genetics of biofuel traits, formulating suitable breeding strategies and seed enhancement techniques to achieve higher productivity in marginal lands in order to avoid food vs. fuel conflict, and finally realization of bioethanol by involving bioengineering process. Many reviews, worldwide researches, and policy papers accepted that sorghum has tremendous potential to be used as a crop of biofuel production.

Bio-Mercury Remediation Suitability Index: A Novel Proposal That Compiles the PGPR Features of Bacterial Strains and Its Potential Use in Phytoremediation.

Soil pollution from heavy metals, especially mercury, is an environmental problem for human health. Biological approaches offer interesting tools, which necessarily involve the selection of organisms capable of transforming the environment via bioremediation. To evaluate the potential use of microorganisms in phytorhizoremediation, bacterial strains were isolated from rhizospheric and bulk soil under conditions of chronic natural mercury, which were identified and characterized by studying the following: (i) their plant growth promoting rhizobacteria (PGPR) activities; and (ii) their maximum bactericide concentration of mercury. Information regarding auxin production, phosphate solubilization, siderophore synthesis and 1-aminocyclopropane-1-carboxylic acid deaminase (ACCd) capacity of the isolates was compiled in order to select the strains that fit potential biotechnological use. To achieve this objective, the present work proposes the Bio-Mercury Remediation Suitability Index (BMR-SI), which reflects the integral behavior of the strains for heavy metal polluted soil bioremediation. Only those strains that rigorously fulfilled all of the established criteria were selected for further assays.

Energetic constraints on mammalian distribution areas.

Energy is a universal resource essential for all life functions. The rate of transformation of energy into an organism, and the energetic investment into reproduction, determines population and ecological-level processes. Several hypotheses predicted that the ecological expansion and size of the geographic distribution of a species are shaped by, among other factors, metabolic performance. However, how organismal energetic characteristics contribute to species geographic range size is poorly understood. With phylogenetic comparative methods whether energetic maintenance costs (basal metabolic rate, BMR), aerobic capacity (maximum exercise metabolic rate, VO2 max), summit thermoregulation (summit metabolic rate, VO2 sum) and the ability to sustain energy provisioning (daily energy expenditure, DEE) determine the distribution of mammalian species range sizes was tested. Both basal and maximum exercise metabolic rates (accounting for body mass), but not summit thermogenic metabolic rate, were positively associated with species range sizes. Furthermore, daily energy expenditure (accounting for body mass) was positively associated with species ranges. Body mass (accounting for energetic maintenance) was negatively related to range sizes. High aerobic exercise capacity, aiding mobility such as running and dispersal, and high sustained energy provisioning, aiding reproductive effort such as pregnancy, lactation and natal dispersal, can facilitate the establishment of large mammalian geographic ranges. Consequently, the pace of organismal physiological processes can shape important ecological and biodiversity patterns by setting limits to species' range sizes.