Ne System Research Articles

Functional specificity of the locus coeruleus-norepinephrine system in the attentional networks

GENERAL COMMENTARY article Front. Behav. Neurosci., 12 December 2013Sec. Learning and Memory Volume 7 - 2013 | https://doi.org/10.3389/fnbeh.2013.00201

Maternal separation increases GABAA receptor-mediated modulation of norepinephrine release in the hippocampus of a rat model of ADHD, the spontaneously hypertensive rat

Experiencing early life stress increases the risk of developing a psychiatric disorder later in life, possibly by altering neural networks, such as the locus-coeruleus norepinephrine (LC–NE) system. Whether early life stress affects the LC–NE system directly, or whether the effects are via changes in glutamate and GABA modulation of the LC–NE system, is unclear. Early life stress has been shown to alter glutamate and GABA transmission, and in particular, to alter GABAA receptor expression. The LC–NE system has been implicated in attention-deficit/hyperactivity disorder (ADHD), amongst other disorders, and is over-responsive to glutamate stimulation in a validated rat model of ADHD, the spontaneously hypertensive rat (SHR). It is plausible that the LC–NE system, or glutamate and GABA modulation thereof, in an individual already genetically predisposed to develop ADHD, or in SHR, may respond in a unique way to early life stress. To investigate this we applied a mild developmental stressor, maternal separation, onto SHR, and onto their control strain, Wistar-Kyoto rats (WKY), from post-natal day (P)2–14. On P50–52, in early adulthood, we assayed glutamate and potassium stimulated release of radio-actively labelled NE (3[H]NE) from hippocampal slices using an in vitro superfusion technique, in the presence or absence of a GABAA receptor antagonist, bicuculline. Our results show that maternal separation altered GABAA receptor-mediated modulation of NE release in the hippocampus of the two strains in opposite directions, increasing it in SHR and decreasing it in WKY. Our findings indicate that effects of early life stress are highly dependent on genetic predisposition, since opposite changes in GABAA receptor-mediated modulation of NE release were observed in the rat model of ADHD, SHR, and their control strain, WKY.

Function and innervation of the locus ceruleus in a macaque model of Functional Hypothalamic Amenorrhea

A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afterwards, the animals were rested until normal menstrual cycles resumed and then euthanized on day 5 of a new menstrual cycle [a] in the absence of further stress; or [b] after 5days of resumed psychosocial and metabolic stress. In this study, parameters of the LC were examined in HSR and SS animals in the presence and absence of stress (2×2 block design) using ICC and image analysis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the synthesis of catecholamines; and the TH level was used to assess by inference, NE output. The pixel area of TH-positive dendrites extending outside the medial border of the LC was significantly increased by stress to a similar degree in both HSR and SS animals (p<0.0001). There is a significant CRF innervation of the LC. The positive pixel area of CRF boutons, lateral to the LC, was higher in SS than HSR animals in the absence of stress. Five days of moderate stress significantly increased the CRF-positive bouton pixel area in the HSR group (p<0.02), but not in the SS group. There is also a significant serotonin innervation of the LC. A marked increase in medial serotonin dendrite swelling and beading was observed in the SS+stress group, which may be a consequence of excitotoxicity. The dendrite beading interfered with analysis of axonal boutons. However, at one anatomical level, the serotonin-positive bouton area was obtained between the LC and the superior cerebellar peduncle. Serotonin-positive bouton pixel area was significantly higher in HSR than SS animals (p<0.04). There was no change in either group after 5days of moderate stress. The ratio of serotonin/TH correlates with ovarian estrogen production with a sensitivity×stress interaction. Therefore, it appears that the serotonin system determines stress sensitivity and the NE system responds to stress. We hypothesize that elevated NE with low serotonin functionality ultimately leads to stress-induced infertility. In contrast, high serotonin functionality maintains ovulation in the presence of stress even with elevated NE.

Effect of the dietary net energy concentration on feed intake and performance of growing-finishing pigs housed individually1

The effect of dietary NE content on feed intake and performance of pigs was investigated using crossbred barrows with initial and final BW of approximately 35 and 110 kg, respectively. Pigs were housed individually and allowed ad libitum access to feed. Pigs were randomly allotted to 6 wheat and soybean meal-based diets (8.1, 8.7, 9.3, 9.9, 10.5, and 11.1 MJ NE/kg) with 16 pigs/diet. Ratios between standardized ileal digestible AA and NE were similar in all diets. Over the entire experiment, increase in dietary NE concentration was associated with a decreased ADFI (3.216, 3.216, 3.122, 2.910, 2.732, and 2.684 kg/d, respectively, for diets containing 8.1 to 11.1 MJ NE/kg; linear, P < 0.01). The NE intake increased as dietary NE increased from 8.1 to 11.1 MJ NE/kg (26.04, 27.98, 29.03, 28.81, 28.68, and 29.77 MJ/d, respectively; linear, P < 0.01, and quadratic, P = 0.06). Average daily gain increased when dietary NE concentration increased (1.046, 1.126, 1.135, 1.177, 1.156, and 1.152 kg/d, respectively, for diets containing 8.1 to 11.1 MJ NE/kg; linear and quadratic, P < 0.01). The increase in dietary NE concentration was associated with an increase in dressing percentage (76.5, 77.0, 77.4, 78.0, 78.2, and 78.4% of BW; linear, P < 0.01) but no differences in lean percentage (58.3, 57.9, 58.0, 57.3, 58.1, and 56.4% of HCW, respectively, for diets containing 8.1 to 11.1 MJ NE/kg; P = 0.12). When dietary NE concentration increased from 8.1 to 11.1 MJ/kg, the G:F increased (0.326, 0.352, 0.364, 0.405, 0.425, and 0.428 kg/kg, respectively; linear, P < 0.01), but the G:F expressed using the NE system did not change (G:F, 39.97 g/MJ NE; P = 0.44). When adjusted to the same dressing yield and lean percentage, the differences in adjusted ADG increased among treatments, but the adjusted G:F expressed using the NE system was not influenced by dietary energy concentration. These results confirm the ability of individually housed pigs to adjust their spontaneous feed intake over a very wide range of NE concentrations (8.7 to 10.5 MJ/kg). Under commercial conditions, pigs may experience less variation in ADFI than the results obtained in this experiment because of differences in dietary energy concentrations. However, it seems that only a severe reduction in dietary energy concentration will be effective in restricting energy intake of pigs that are allowed ad libitum access to feed.

Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure

The cannabinoid receptor agonist, WIN 55,212-2, increases extracellular norepinephrine levels in the rat frontal cortex under basal conditions, likely via desensitization of inhibitory α2-adrenergic receptors located on norepinephrine terminals. Here, the effect of WIN 55,212-2 on stress-induced norepinephrine release was assessed in the medial prefrontal cortex (mPFC), in adult male Sprague–Dawley rats using in vivo microdialysis. Systemic administration of WIN 55,212-2 30min prior to stressor exposure prevented stress-induced cortical norepinephrine release induced by a single exposure to swim when compared to vehicle. To further probe cortical cannabinoid–adrenergic interactions, postsynaptic α2-adrenergic receptor (AR)-mediated responses were assessed in mPFC pyramidal neurons using electrophysiological analysis in an in vitro cortical slice preparation. We confirm prior studies showing that clonidine increases cortical pyramidal cell excitability and that this was unaffected by exposure to acute stress. WIN 55,212-2, via bath application, blocked postsynaptic α2-AR mediated responses in cortical neurons irrespective of exposure to stress. Interestingly, stress exposure prevented the desensitization of α2-AR mediated responses produced by a history of cannabinoid exposure. Together, these data indicate the stress-dependent nature of cannabinoid interactions via both pre- and postsynaptic ARs. In summary, microdialysis data indicate that cannabinoids restrain stress-induced cortical NE efflux. Electrophysiology data indicate that cannabinoids also restrain cortical cell excitability under basal conditions; however, stress interferes with these CB1–α2 AR interactions, potentially contributing to over-activation of pyramidal neurons in mPFC. Overall, cannabinoids are protective of the NE system and cortical excitability but stress can derail this protective effect, potentially contributing to stress-related psychopathology. These data add to the growing evidence of complex, stress-dependent modulation of monoaminergic systems by cannabinoids and support the potential use of cannabinoids in the treatment of stress-induced noradrenergic dysfunction.

Carbapenemase-producingAcinetobacterspp. in Cattle, France

To the Editor: Multidrug resistance in bacteria isolated from animals is an emerging phenomenon, mirroring what is happening among humans. During the past decade, expanded-spectrum β-lactamases in Enterobacteriaceae from humans (1) and animals (2) worldwide have been reported. Among humans, as a consequence of this high rate, use of carbepenems is increasing selection pressure; carbapenem-resistant gram-negative organisms are increasingly reported, including carbapenemase-producing Enterobacteriaceae and Acinetobacter spp (3). The most commonly acquired carbapenemases identified in Acinetobacter spp. correspond to carbapenem-hydrolyzing class D β-lactamases (3). In particular, the worldwide spread of OXA-23–producing A. baumannii is considered a serious threat; those strains are frequently involved in nosocomial outbreaks for which therapeutic options are extremely limited (3,4). Our study objective was to evaluate the possible occurrence of carbapenemase-producing gram-negative bacteria in dairy cattle in France. In August 2010, at a dairy farm 30 km from Paris, France, rectal swabs were collected from 50 cows. Samples were precultured in buffered peptone water and incubated for 18 h at 37°C. Cultures were inoculated by streaking 100 μL of the suspensions onto Drigalski agar plates (bioMerieux, Balmes-les-Grottes, France) containing 1 μg/mL of imipenem to select for carbapenem-resistant gram-negative isolates. Of the 50 samples, 9 produced growth on imipenem-containing plates. All colonies tested (10 colonies/sample) by using the API 20 NE (bioMerieux) system were first identified as A. lwoffii. Molecular techniques based on sequencing of the gyrA, gyrB, and rpoB genes (5) enabled more precise identification and indicated that all isolates belonged to the Acinetobacter genomospecies (DNA group) 15TU, which is known to be phylogenetically related to A. lwoffii and which has been reportedly isolated from sewage, freshwater aquaculture habitats, trout intestines, and frozen shrimp (6). One colony per sample was retained for further investigation (isolates BY1 to BY9). Susceptibility testing and MIC determinations were performed by disk-diffusion assay (Sanofi-Diagnostic Pasteur, Marnes-la-Coquette, France) and Etest (AB bioMerieux, Solna, Sweden) (Table). All isolates except 1 were resistant to penicillins, combinations of penicillins and β-lactamase inhibitors, and carbapenems but susceptible to cefotaxime and of reduced susceptibility to ceftazidime. Isolate BY1 showed higher MICs for carbapenems (Table). In addition, all isolates were resistant to tetracycline, kanamycin, and fosfomycin and remained susceptible to fluoroquinolones, chloramphenicol, gentamicin, amikacin, tobramycin, and sulfonamides. Susceptibility profiles of 3 Acinetobacter genomospecies 15TU reference strains showed that they were fully susceptible to penicillins, carbapenems, tetracycline, and kanamycin. Table Antimicrobial drug MICs for Acinetobacter genomospecies 15TU isolates from cows and reference strains, France, August 2010 Clonal diversity between the isolates was assessed by pulsed-field gel electrophoresis (5), which showed 6 distinct genotypes. Isolate BY1 corresponded to a single clone (data not shown), which indicated that the occurrence of Acinetobacter genomospecies 15TU strains among these animals was not the result of dissemination of a single clone. PCR detection and sequencing of genes that encode carbapenem-hydrolyzing class D β-lactamases (5) showed that the 9 Acinetobacter genomospecies 15TU isolates harbored a blaOXA-23 gene, whereas the 3 reference strains remained negative. Sequencing confirmed that all isolates expressed β-lactamase OXA-23, which is known to be widespread in A. baumannii. Mating-out assays and plasmid electroporation assays were performed by using blaOXA-23–positive Acinetobacter spp. isolates as donors and rifampin-resistant A. baumannii BM4547 isolates as a recipient strain (5); however, these assays were unsuccessful. Plasmid DNA analysis (5) gave uninterpretable results, with DNA degradations. The genetic structures surrounding the blaOXA-23 gene were investigated by PCR mapping (7), which identified transposon Tn2008 in isolate BY2 only. Tn2008 is a major vehicle for the spread of the blaOXA-23 gene in A. baumannii in the People’s Republic of China (8) and the United States (9). In the other isolates, the ISAba1 element of Tn2008 had been truncated by a novel insertion sequence termed ISAcsp2 (www-is.biotoul.fr). The dairy farmer indicated that most animals from which OXA-23 producers had been identified had received antimicrobial drugs in the previous weeks. Although 1 animal had received amoxicillin-clavulanate, most of the others had been given oxytetracycline and neomycin to treat mastitis. β-lactamase OXA-23 is a common source of carbapenem resistance in A. baumannii (5). Infections with multidrug-resistant OXA-23–producing A. baumannii or A. junii have been reported from hospitals but not from the community. Our study showed that OXA-23–producers in particular, and carbapenemase producers in general, may be isolated from animals. Among the hypotheses that could explain the selection of this carbapenemase, use of penicillins or penicillin–β-lactamase inhibitor combinations could create selective pressure for β-lactamases because OXA-23 does confer, in addition to decreased susceptibility to carbapenems, a high level of resistance to those compounds. We have previously shown that A. radioresistens, an environmental species, was the progenitor of the blaOXA-23 gene (10). Studies are needed to determine to what extent and at which locations Acinetobacter genomospecies 15TU and A. radioresistens might co-reside and therefore where the blaOXA-23 gene exchange might have occurred.

The Impact of Deliberative Strategy Dissociates ERP Components Related to Conflict Processing vs. Reinforcement Learning

We applied the event-related brain potential (ERP) technique to investigate the involvement of two neuromodulatory systems in learning and decision making: The locus coeruleus–norepinephrine system (NE system) and the mesencephalic dopamine system (DA system). We have previously presented evidence that the N2, a negative deflection in the ERP elicited by task-relevant events that begins approximately 200 ms after onset of the eliciting stimulus and that is sensitive to low-probability events, is a manifestation of cortex-wide noradrenergic modulation recruited to facilitate the processing of unexpected stimuli. Further, we hold that the impact of DA reinforcement learning signals on the anterior cingulate cortex (ACC) produces a component of the ERP called the feedback-related negativity (FRN). The N2 and the FRN share a similar time range, a similar topography, and similar antecedent conditions. We varied factors related to the degree of cognitive deliberation across a series of experiments to dissociate these two ERP components. Across four experiments we varied the demand for a deliberative strategy, from passively watching feedback, to more complex/challenging decision tasks. Consistent with our predictions, the FRN was largest in the experiment involving active learning and smallest in the experiment involving passive learning whereas the N2 exhibited the opposite effect. Within each experiment, when subjects attended to color, the N2 was maximal at frontal–central sites, and when they attended to gender it was maximal over lateral-occipital areas, whereas the topology of the FRN was frontal–central in both task conditions. We conclude that both the DA system and the NE system act in concert when learning from rewards that vary in expectedness, but that the DA system is relatively more exercised when subjects are relatively more engaged by the learning task.

Characterization and control of microbial black spot spoilage in dry-cured Iberian ham

The presence of black spots on dry-cured Iberian ham surface is an alteration related to microbial population. Although it provokes important economic losses for the meat industry, the microorganisms responsible for this spoilage still remain unclear. The aim of this study was to identify the microorganisms involved in dry-cured Iberian ham black spot spoilage and to study the conditions affecting their growth. Several microbial strains were isolated from Iberian hams spoiled with black spots at the beginning of post-salting stage. However just one strain produced black coloration in both culture media and fat from Iberian ham. This strain was tentatively identified as Pseudomonas fluorescens by using the API 20 NE system and phylogenetic analyses based on the 16S rRNA and carA genes. It was able to grow and produce blackening at 5, 25, and 30 °C and with salt concentrations of 2 and 5% at 25 °C and with 2% NaCl at 5 °C in culture media. When it was inoculated in sterile pork fat tissues, grow and blackening were only detected in samples without added salt at water activity of 0.94 and 0.97. In order to control the incidence of the alteration temperature throughout salting and post-salting stages should be under 5 °C until salt reaches at least a concentration of 2% or water activity is reduced on the surface of dry-cured Iberian ham below 0.92.

Pupil Diameter Predicts Changes in the Exploration–Exploitation Trade-off: Evidence for the Adaptive Gain Theory

The adaptive regulation of the balance between exploitation and exploration is critical for the optimization of behavioral performance. Animal research and computational modeling have suggested that changes in exploitative versus exploratory control state in response to changes in task utility are mediated by the neuromodulatory locus coeruleus-norepinephrine (LC-NE) system. Recent studies have suggested that utility-driven changes in control state correlate with pupil diameter, and that pupil diameter can be used as an indirect marker of LC activity. We measured participants' pupil diameter while they performed a gambling task with a gradually changing payoff structure. Each choice in this task can be classified as exploitative or exploratory using a computational model of reinforcement learning. We examined the relationship between pupil diameter, task utility, and choice strategy (exploitation vs. exploration), and found that (i) exploratory choices were preceded by a larger baseline pupil diameter than exploitative choices; (ii) individual differences in baseline pupil diameter were predictive of an individual's tendency to explore; and (iii) changes in pupil diameter surrounding the transition between exploitative and exploratory choices correlated with changes in task utility. These findings provide novel evidence that pupil diameter correlates closely with control state, and are consistent with a role for the LC-NE system in the regulation of the exploration-exploitation trade-off in humans.

Orienting of attention, pupil size, and the norepinephrine system

This research examined a novel suggestion regarding the involvement of the locus coeruleus-norepinephrine (LC-NE) system in orienting reflexive (exogenous) attention. A common procedure for studying exogenous orienting of attention is Posner's cuing task. Importantly, one can manipulate the required level of target processing by changing task requirements, which, in turn, can elicit a different time course of inhibition of return (IOR). An easy task (responding to target location) produces earlier onset IOR, whereas a demanding task (responding to target identity) produces later onset IOR. Aston-Jones and Cohen (Annual Review of Neuroscience, 28, 403-450, 2005) presented a theory suggesting two different modes of LC activity: tonic and phasic. Accordingly, we suggest that in the more demanding task, the LC-NE system is activated in phasic mode, and in the easier task, it is activated in tonic mode. This, in turn, influences the appearance of IOR. We examined this suggestion by measuring participants' pupil size, which has been demonstrated to correlate with the LC-NE system, while they performed cuing tasks. We found a response-locked phasic dilation of the pupil in the discrimination task, as compared with the localization task, which may reflect different firing modes of the LC-NE system during the two tasks. We also demonstrated a correlation between pupil size at the time of cue presentation and magnitude of IOR.

The role of the noradrenergic system in the exploration-exploitation trade-off: a pharmacological study

Animal research and computational modeling have indicated an important role for the neuromodulatory locus coeruleus–norepinephrine (LC–NE) system in the control of behavior. According to the adaptive gain theory, the LC–NE system is critical for optimizing behavioral performance by regulating the balance between exploitative and exploratory control states. However, crucial direct empirical tests of this theory in human subjects have been lacking. We used a pharmacological manipulation of the LC–NE system to test predictions of this theory in humans. In a double-blind parallel-groups design (N = 52), participants received 4 mg reboxetine (a selective norepinephrine reuptake inhibitor), 30 mg citalopram (a selective serotonin reuptake inhibitor), or placebo. The adaptive gain theory predicted that the increased tonic NE levels induced by reboxetine would promote task disengagement and exploratory behavior. We assessed the effects of reboxetine on performance in two cognitive tasks designed to examine task (dis)engagement and exploitative versus exploratory behavior: a diminishing-utility task and a gambling task with a non-stationary pay-off structure. In contrast to predictions of the adaptive gain theory, we did not find differences in task (dis)engagement or exploratory behavior between the three experimental groups, despite demonstrable effects of the two drugs on non-specific central and autonomic nervous system parameters. Our findings suggest that the LC–NE system may not be involved in the regulation of the exploration–exploitation trade-off in humans, at least not within the context of a single task. It remains to be examined whether the LC–NE system is involved in random exploration exceeding the current task context.

Validation of Vitek 2 Nonfermenting Gram-Negative Cards and Vitek 2 Version 4.02 Software for Identification and Antimicrobial Susceptibility Testing of Nonfermenting Gram-Negative Rods from Patients with Cystic Fibrosis

Accurate identification and antimicrobial susceptibility testing (AST) of nonfermenters from cystic fibrosis patients are essential for appropriate antimicrobial treatment. This study examined the ability of the newly designed Vitek 2 nonfermenting gram-negative card (NGNC) (new gram-negative identification card; bioMérieux, Marcy-l'Etoile, France) to identify nonfermenting gram-negative rods from cystic fibrosis patients in comparison to reference methods and the accuracy of the new Vitek 2 version 4.02 software for AST compared to the broth microdilution method. Two hundred twenty-four strains for identification and 138 strains for AST were investigated. The Vitek 2 NGNC identified 211 (94.1%) of the nonfermenters correctly. Among morphologically atypical microorganisms, five strains were misidentified and eight strains were determined with low discrimination, requiring additional tests which raised the correct identification rate to 97.8%. Regarding AST, the overall essential agreement of Vitek 2 was 97.6%, and the overall categorical agreement was 92.9%. Minor errors were found in 5.1% of strains, and major and very major errors were found in 1.6% and 0.3% of strains, respectively. In conclusion, the Vitek NGNC appears to be a reliable method for identification of morphologically typical nonfermenters and is an improvement over the API NE system and the Vitek 2 GNC database version 4.01. However, classification in morphologically atypical nonfermenters must be interpreted with care to avoid misidentification. Moreover, the new Vitek 2 version 4.02 software showed good results for AST and is suitable for routine clinical use. More work is needed for the reliable testing of strains whose MICs are close to the breakpoints.

Potential curves and nonadiabatic coupling matrix elements for the O+−Ne system

An ensemble-average one-electron potential is used to define a molecular orbital basis suitable for the simultaneous description of a set of low-lying electronic states. The common basis simplifies the construction of the coupling between different Born-Oppenheimer states, and the required matrix elements are calculated. A new excitation mechanism is developed for inelastic scattering of O+ on Ne.

The differential interference angle of 2∏[Case(a)] diatom on rotational energy transfer in NO (X2∏) collision with He, Ne and Ar system

To study theoretically the relationship between the differential interference angle and the scattering angle in collisional quantum interference (CQI), we have investigated the differential interference angle of the atom–diatomic [case(a)] molecule system in detail. For the 2∏ electronic state in Hund's case (a), the degree of the differential interference is also discussed. The differential interference angles of NO(X2∏) are calculated quantitatively for the rotational energy transfer in Hund's case (a) induced by collision with He, Ne and Ar atoms. The method to calculate the differential interference angle is presented. Several factors that affect the differential interference angle are investigated. Finally the variation of the differential interference angle with the impact parameter and relative velocity is discussed.

ASAS CENTENNIAL PAPER: Net energy systems for beef cattle--Concepts, application, and future models

Development of nutritional energetics can be traced to the 1400s. Lavoisier established relationships among O(2) use, CO(2) production and heat production in the late 1700s, and the laws of thermodynamics and law of Hess were discovered during the 1840s. Those discoveries established the fundamental bases for nutritional energetics and enabled the fundamental entity ME = retained energy + heat energy to be established. Objectives became: 1) to establish relationships between gas exchange and heat energy, 2) to devise bases for evaluation of foods that could be related to energy expenditures, and 3) to establish causes of energy expenditures. From these endeavors, the basic concepts of energy partitioning by animals were developed, ultimately resulting in the development of feeding systems based on NE concepts. The California Net Energy System, developed for finishing beef cattle, was the first to be based on retained energy as determined by comparative slaughter and the first to use 2 NE values (NE(m) and NE(g)) to describe feed and animal requirements. The system has been broadened conceptually to encompass life cycle energy requirements of beef cattle and modified by the inclusion of numerous adjustments to address factors known to affect energy requirements and value of feed to meet those needs. The current NE system remains useful but is empirical and static in nature and thus fails to capture the dynamics of energy utilization by diverse animals as they respond to changing environmental conditions. Consequently, efforts were initiated to develop dynamic simulation models that captured the underlying biology and thus were sensitive to variable genetic and environmental conditions. Development of a series of models has been described to show examples of the conceptual evolution of dynamic, mechanistic models and their applications. Generally with each new system, advances in prediction accuracy came about by adding new terms to conceptually validated models. However, complexity of input requirements often limits general use of these larger models. Expert systems may be utilized to provide many of the additional inputs needed for application of the more complex models. Additional information available from these systems is expected to result in an ever-increasing range of application. These systems are expected to have increased generality and the capability to be integrated with other models to allow economic evaluation. This will eventually allow users to compute solutions that allow development of optimal production strategies.

ASAS CENTENNIAL PAPER: Net energy systems for beef cattle—Concepts, application, and future models1

Development of nutritional energetics can be traced to the 1400s. Lavoisier established relationships among O(2) use, CO(2) production and heat production in the late 1700s, and the laws of thermodynamics and law of Hess were discovered during the 1840s. Those discoveries established the fundamental bases for nutritional energetics and enabled the fundamental entity ME = retained energy + heat energy to be established. Objectives became: 1) to establish relationships between gas exchange and heat energy, 2) to devise bases for evaluation of foods that could be related to energy expenditures, and 3) to establish causes of energy expenditures. From these endeavors, the basic concepts of energy partitioning by animals were developed, ultimately resulting in the development of feeding systems based on NE concepts. The California Net Energy System, developed for finishing beef cattle, was the first to be based on retained energy as determined by comparative slaughter and the first to use 2 NE values (NE(m) and NE(g)) to describe feed and animal requirements. The system has been broadened conceptually to encompass life cycle energy requirements of beef cattle and modified by the inclusion of numerous adjustments to address factors known to affect energy requirements and value of feed to meet those needs. The current NE system remains useful but is empirical and static in nature and thus fails to capture the dynamics of energy utilization by diverse animals as they respond to changing environmental conditions. Consequently, efforts were initiated to develop dynamic simulation models that captured the underlying biology and thus were sensitive to variable genetic and environmental conditions. Development of a series of models has been described to show examples of the conceptual evolution of dynamic, mechanistic models and their applications. Generally with each new system, advances in prediction accuracy came about by adding new terms to conceptually validated models. However, complexity of input requirements often limits general use of these larger models. Expert systems may be utilized to provide many of the additional inputs needed for application of the more complex models. Additional information available from these systems is expected to result in an ever-increasing range of application. These systems are expected to have increased generality and the capability to be integrated with other models to allow economic evaluation. This will eventually allow users to compute solutions that allow development of optimal production strategies.

Glucocorticoid actions on airway epithelial responses in immunity: Functional outcomes and molecular targets

Research on the biology of airway epithelium in the last decades has progressively uncovered the many roles of this cell type during the immune response. Far from the early view of the epithelial layer simply as a passive barrier, the airway epithelium is now considered a central player in mucosal immunity, providing innate mechanisms of first-line host defense as well as facilitating adaptive immune responses. Alterations of the epithelial phenotype are primarily involved in the pathogenesis of allergic airways disease, particularly in severe asthma. Appreciation of the epithelium as target of glucocorticoid therapy has also grown, because of studies defining the pathways and mediators affected by glucocorticoids, and studies illustrating the relevance of the control of the response from epithelium in the overall efficacy of topical and systemic therapy with glucocorticoids. Studies of the mechanism of action of glucocorticoids within the biology of the immune response of the epithelium have uncovered mechanisms of gene regulation involving both transcriptional and posttranscriptional events. The view of epithelium as therapeutic target therefore has plenty of room to evolve, as new knowledge on the role of epithelium in immunity is established and novel pathways mediating glucocorticoid regulation are elucidated.

Net energy evaluation of feeds and determination of net energy requirements for pigs

Feeds for pigs can be attributed different energy values according to, first, the step considered in energy utilization (DE: digestible energy, ME: metabolizable energy and NE: net energy) and, second, the method used for estimation at each step. Reference methods for evaluating DE content are based on in vivo digestibility measurements; indirect estimates of DE values are obtained from in vitro methods or prediction equations based on chemical characteristics. Methods have also been proposed for estimating urinary energy (and gas energy to a smaller extent) in order to calculate ME content from DE value. The NE values originate from energy balance studies (slaughter methods or, more commonly, indirect calorimetry measurements in respiration chambers) and their compilation allows the calculation of NE prediction equations based on digestible nutrient contents or DE or ME contents. Such equations are applicable to both ingredients and compound feeds. They may differ between origins according to the fractionation method of organic matter or assumptions such as the NE requirement for maintenance (or fasting heat production). These measurements represent the bases for establishment of energy values in feeding tables. Results indicate that energy digestibility of feeds is negatively affected by dietary fibre content but this negative effect is attenuated with body weight increase, which suggests that feeds should be attributed DE values according to pig BW; in practice, at least two different DE values, one for growing-finishing pigs and one for mature pigs (reproductive sows), are recommended. The energy digestibility of pig feeds can also be affected by feed processing (pelletting, extrusion, etc.). Efficiency of ME utilization for NE averages 74-75% for conventional pig diets but it is directly dependent on diet chemical composition with efficiencies higher for ME from fat (90%) or starch (82%) than from protein or dietary fibre (60%). The hierarchy between feeds and results of least-cost formulation are then dependent on the energy system with overestimation of protein rich feeds and underestimation of starch and/or fat rich feeds in the DE or ME systems. The NE system provides an energy value which is the closest estimate of the "true" energy value of a feed; it predicts more accurately the performance of the pigs and allows implementing new feeding approaches such as the use of low protein and/or high fat diets. Energy requirements expressed as DE or ME can be transformed to NE requirements if we assume that the average efficiencies of DE or ME for NE are 71 and 74%, respectively. More sophisticated methods including modeling techniques can also be used for evaluating energy requirements.

Ethiological structure and epidemiological monitoring of bacterial infections in industrially reared birds in Bulgaria

The study was performed on the 9 largest poultry farms and hatcheries in Bulgaria during the period from 2001 to 2006. Eight hundred thirty three samples from birds have been investigated seven hundred ten from gallinaceous and one hundred twenty three from waterfowl. The samples have been taken from corpse material (liver, spleen, joint, air sack, small intestine) as well from dead embryo, cloacal and nasal swabs. They were analyzed using routine laboratory or the semi-automatic system of identification CRYSTAL for enterobacteriae and staphylococci, as well as using the API-20 NE system for nonfermentative bacteria. A positive microbial finding was current in 67.8% of samples from dead chick embryos. The isolates belong to 13 different microbial species. A total of 14 species were isolated from the corpse material, nasal and cloacal swabs. Their specific presence is age dependent. Similar results have been found for waterfowl.

Bacterial Identification, Clinical Significance, and Antimicrobial Susceptibilities of Acinetobacter ursingii and Acinetobacter schindleri , Two Frequently Misidentified Opportunistic Pathogens

The species belonging to the Acinetobacter genus are currently reported as opportunistic pathogens in hospitalized patients with underlying predispositions. However, except for the Acinetobacter calcoaceticus-Acinetobacter baumannii complex, the identification of other species is frequently unreliable, especially for Acinetobacter ursingii and Acinetobacter schindleri, newly described in 2001. Thus, the clinical significance, phenotypic features, and antimicrobial susceptibilities of these two misidentified species remain unclear. Of 456 Acinetobacter sp. clinical strains isolated from 2002 to 2005 in Henri Mondor Hospital, 15 isolates (10 A. ursingii and 5 A. schindleri isolates) were studied. They were characterized using a phenotypic approach (API 20 NE and VITEK 2 systems), 16S rRNA gene sequencing, and susceptibility to antimicrobial agents with evaluation of impact in clinical relevance. The two corresponding type strains were also included for comparison. All isolates were identified to the species level using molecular tools, whereas the phenotypic methods remained unreliable due to the absence of these two species in the manufacturers' databases. However, the API 20 NE system appeared to be a reasonably reliable phenotypic alternative for the identification of A. ursingii when the numerical code 0000071 was found. Conversely, no discriminative phenotypic alternative existed for A. schindleri isolates. Concerning antimicrobial susceptibility, A. ursingii strains appeared to be more resistant to antibiotics than A. schindleri strains, which could imply therapeutic consequences. Finally, the prevalence of infections caused by A. ursingii and A. schindleri (representing 9.7% and 4.8% of non-A. calcoaceticus-A. baumannii complex strains, respectively) seems to be underestimated.