Enhanced Erythrocyte Adhesiveness/Aggregation in Obesity Corresponds to Low‐Grade Inflammation

Objective: Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and to assess phosphatidylserine expression on erythrocyte surface membrane of obese vs. nonobese individuals. Research Methods and Procedures: Erythrocyte adhesiveness/aggregation in the peripheral venous blood was evaluated by using a new biomarker, phosphatidylserine expression was assessed by means of flow cytometry, and markers of inflammation were measured in 65 subjects: 30 obese [body mass index (BMI) = 41 ± 7.7 kg/m²] and 35 nonobese (BMI = 24 ± 2.7 kg/m²) individuals. Pearson correlations and Student's t test were performed. Results: A highly significant difference was noted in the degree of erythrocyte adhesiveness/aggregation and markers of inflammation between the study groups. BMI correlated with erythrocyte adhesiveness/aggregation (r = 0.42, p = 0.001), erythrocyte sedimentation rate (r = 0.42, p = 0.001), high‐sensitive C‐reactive protein (r = 0.55, p < 10^?4), fibrinogen (r = 0.37, p = 0.004), and white blood cell count (r = 0.45, p < 10^?4). The degree of erythrocyte adhesiveness/aggregation correlated with erythrocyte sedimentation rate (r = 0.5, p < 10^?4), high‐sensitive C‐reactive protein (r = 0.56, p < 10^?4), fibrinogen (r = 0.54, p < 10^?4), and white blood cell count (r = 0.32, p = 0.01). Discussion: Our results suggest that obesity‐related erythrocyte adhesiveness/aggregation is probably mediated through increased concentrations of adhesive macromolecules in the circulation and not necessarily through hyperlipidemia or phosphatidylserine exposure on erythrocyte's membrane.     

Glucose Kinetics in the Collagen-Induced Arthritis Model: An All-in-One Model to Assess Both Efficacy and Metabolic Side Effects of Glucocorticoids

Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory drugs, but chronic use is hampered by metabolic side effects. Therefore, there is an urgent medical need for improved GCs that are as effective as classical GCs but have a better safety profile. A well-established model to assess anti-inflammatory efficacy is the chronic collagen-induced arthritis (CIA) model in mice, a model with features resembling rheumatoid arthritis. Models to quantify undesired effects of glucocorticoids on glucose kinetics are less well-established. Recently, we have described a model to quantify basal blood glucose kinetics using stably-labeled glucose. In the present study, we have integrated this blood glucose kinetic model in the CIA model to enable quantification of both efficacy and adverse effects in one animal model. Arthritis scores were decreased after treatment with prednisolone, confirming the anti-inflammatory properties of GCs. Both inflammation and prednisolone induced insulin resistance as insulin secretion was strongly increased whereas blood glucose concentrations and hepatic glucose production were only slightly decreased. This insulin resistance did not directly resulted in hyperglycemia, indicating a highly adaptive compensatory mechanism in these mice. In conclusion, this ‘all-in-one’ model allows for studying effects of (novel) GC compounds on the development of arthritis and glucose kinetics in a single animal. This integrative model provides a valuable tool for investigating (drug-induced) metabolic dysregulation in an inflammatory setting.     

Vulnerability of Mediterranean Ecosystems to Long-Term Changes along the Coast of Israel

Although human activity is considered to be a major driving force affecting the distribution and dynamics of Mediterranean ecosystems, the full consequences of projected climate variability and relative sea-level changes on fragile coastal ecosystems for the next century are still unknown. It is unclear how these waterfront ecosystems can be sustained, as well as the services they provide, when relative sea-level rise and global warming are expected to exert even greater pressures in the near future (drought, habitat degradation and accelerated shoreline retreat). Haifa Bay, northern Israel, has recorded a landward sea invasion, with a maximum sea penetration 4,000 years ago, during an important period of urban development and climate instability. Here, we examine the cumulative pressure of climate shifts and relative sea-level changes in order to investigate the patterns and mechanisms behind forest replacement by an open-steppe. We provide a first comprehensive and integrative study for the southern Levant that shows that (i) human impact, through urbanization, has been the main driver behind ecological erosion in the past 4,000 years; (ii) climate pressures have reinforced this impact; and (iii) local coastal changes have played a decisive role in eroding ecosystem resilience. These three parameters, which have closely interacted during the last 4,000 years in Haifa Bay, clearly indicate that for an efficient management of the coastal habitats, anthropogenic pressures linked to urban development must be reduced in order to mitigate the predicted effects of Global Change.     

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.     

Cytokinins Increase Epicatechin Content and Fungal Decay Resistance in Avocado Fruits

   apd: 7 June 2001     

Ontogenetic shifts in plant–plant interactions in a rare cycad within angiosperm communities

Gymnosperms and angiosperms can co-occur within the same habitats but key plant traits are thought to give angiosperms an evolutionary competitive advantage in many ecological settings. We studied ontogenetic changes in competitive and facilitative interactions between a rare gymnosperm (Dioon sonorense, our target species) and different plant and abiotic neighbours (conspecific-cycads, heterospecific-angiosperms, or abiotic-rocks) from 2007 to 2010 in an arid environment of northwestern Mexico. We monitored survival and growth of seedlings, juveniles, and adults of the cycad Dioon sonorense to evaluate how cycad survival and relative height growth rate (RHGR) responded to intra- and interspecific competition, canopy openness, and nearest neighbour. We tested spatial associations among D. sonorense life stages and angiosperm species and measured ontogenetic shifts in cycad shade tolerance. Canopy openness decreased cycad survival while intraspecific competition decreased survival and RHGR during early ontogeny. Seedling survival was higher in association with rocks and heterospecific neighbours where intraspecific competition was lower. Shade tolerance decreased with cycad ontogeny reflecting the spatial association of advanced stages with more open canopies. Interspecific facilitation during early ontogeny of our target species may promote its persistence in spite of increasing interspecific competition in later stages. We provide empirical support to the long-standing assumption that marginal rocky habitats serve as refugia from angiosperm competition for slow-growing gymnosperms such as cycads. The lack of knowledge of plant–plant interactions in rare or endangered species may hinder developing efficient conservation strategies (e.g. managing for sustained canopy cover), especially under the ongoing land use and climatic changes.     

Factors affecting abundance of Triaenophorus infection in Cyclops strenuus, and parasite-induced changes in host fitness

Factors affecting the abundance of Triaenophorus crassus and Triaenophorus nodulosus procercoids in their copepod first intermediate host, Cyclops strenuus, and effects of infection on feeding behaviour, reproduction and survival of the host were studied experimentally. When exposed to the same number of coracidia, copepods harboured considerably less procercoids in the trials where ciliates or Artemia salina nauplii were given as alternative food items. The prevalence of infection was higher in adult copepods as compared with copepodite stage IV and stage V, and higher in stage V than in stage IV. The prevalences in adult females and males did not differ significantly from each other. The frequency of females carrying egg sacs was lower among infected than among exposed uninfected and unexposed copepods. The rate of feeding on Artemia nauplii remained at the same level in uninfected copepods, but decreased strongly in infected copepods during 7 days p.i. The survival of unexposed, exposed uninfected and infected copepods did not differ significantly from each other for the first 11 days post-exposure, but the mortality of infected copepods increased significantly after 3 weeks post-exposure. However, the rate of development and mortality of copepods might have been affected by the apparently arrested development of stage IV copepodites found in the experiment. Some of the contradictions between these results and earlier observations are suggested to be caused by the differences in the duration of exposure, intensity of infection and duration of observation post-exposure in the present study as compared with other experiments.     

Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice

Gene targeting was used to delete exon 2 of mouse DOR-1, which encodes the delta opioid receptor. Essentially all 3H-[D-Pen2,D-Pen5]enkephalin (3H-DPDPE) and 3H-[D-Ala2,D-Glu4]deltorphin (3H-deltorphin-2) binding is absent from mutant mice, demonstrating that DOR-1 encodes both delta1 and delta2 receptor subtypes. Homozygous mutant mice display markedly reduced spinal delta analgesia, but peptide delta agonists retain supraspinal analgesic potency that is only partially antagonized by naltrindole. Retained DPDPE analgesia is also demonstrated upon formalin testing, while the nonpeptide delta agonist BW373U69 exhibits enhanced activity in DOR-1 mutant mice. Together, these findings suggest the existence of a second delta-like analgesic system. Finally, DOR-1 mutant mice do not develop analgesic tolerance to morphine, genetically demonstrating a central role for DOR-1 in this process.     

Comparison of anionic and cationic trypsinogens: the anionic activation domain is more flexible in solution and differs in its mode of BPTI binding in the crystal structure

Unlike bovine cationic trypsin, rat anionic trypsin retains activity at high pH. This alkaline stability has been attributed to stabilization of the salt bridge between the N-terminal Ile16 and Asp194 by the surface negative charge (Soman K, Yang A-S, Honig B, Fletterick R., 1989, Biochemistry 28:9918-9926). The formation of this salt bridge controls the conformation of the activation domain in trypsin. In this work we probe the structure of rat trypsinogen to determine the effects of the surface negative charge on the activation domain in the absence of the Ile16-Asp194 salt bridge. We determined the crystal structures of the rat trypsin-BPTI complex and the rat trypsinogen-BPTI complex at 1.8 and 2.2 A, respectively. The BPTI complex of rat trypsinogen resembles that of rat trypsin. Surprisingly, the side chain of Ile16 is found in a similar position in both the rat trypsin and trypsinogen complexes, although it is not the N-terminal residue and cannot form the salt bridge in trypsinogen. The resulting position of the activation peptide alters the conformation of the adjacent autolysis loop (residues 142-153). While bovine trypsinogen and trypsin have similar CD spectra, the CD spectrum of rat trypsinogen has only 60% of the intensity of rat trypsin. This lower intensity most likely results from increased flexibility around two conserved tryptophans, which are adjacent to the activation domain. The NMR spectrum of rat trypsinogen contains high field methyl signals as observed in bovine trypsinogen. It is concluded that the activation domain of rat trypsinogen is more flexible than that of bovine trypsinogen, but does not extend further into the protein core.     

Immunomodulatory effect of selenosemicarbazides and selenium inorganic compounds, distribution in organs after selenium supplementation

Antioxidant properties of selenium producing a protective barrier against free radicals play an important role in numerous metabolic and immunologic processes associated with oxidation- reduction reactions which take place during intracellular digestion of phagocyted bacteria. The aim of our study was to examine the properties of an organic compound of selenium, 4-(o-tolilo)- selenosemicarbazide of p-chlorobenzoic acid in terms of its retention in organs, effect on erythropoesis and phagocytic abilities of neutrophiles as well as antioxidant properties in neutrophiles tested with NBT test. This compound as well as inorganic sodium selenate was given to Swiss mice at the dose of 10^–3 g Se/kg for the period of 10 days. The concentrations of selenium in livers of mice treated with sodium selenate and selenosemicarbazide were found to be higher than in controls (18,7 g lg^–1 and 23.2 g lg^–1 vs. 12 g lg^–1, respectively). Analysis of blood cells count has shown a significant decrease in neutrophile levels in both groups treated with selenium. The influence of selenium compounds on phagocytosis and especially NBT test has been determined (3.8% of positive cells in the controls vs. 2.2% and 0.9% in the groups treated with sodium selenate and selenosemicarbazide, respectively). Our preliminary investigations suggest that selenosemicarbazides are biologically active compounds and can modify neutrophile functions.