Influence of dietary mannanoligosaccharides on histological parameters of the jejunal mucosa and growth performance of broiler chickens

The trial involved 480 Hubbard Classic broiler chicks which were from either mannanoligosaccharide (MOS) fed breeder flock (Bio-Mos, Alltech Inc. USA at level of 1 kg/t) or control fed breeder flock (without MOS). Three groups with four replicates per treatment were formed: control fed breeders/control fed broilers (C/C); MOS fed breeders/control fed broilers (BM/C) and MOS fed breeders/MOS fed broilers (BM/BM). All chicks were fed the same basal diet, except for the inclusion of Bio-Mos (1, 0.75 and 0.5 kg/t in the starter, grower and finisher diet, respectively). The results showed a significant improvement (p<0.05) in the body weight gain with the addition of Bio-Mos in broiler feed. Feed conversion ratio was improved by 0.03 points, but the difference was not significant (P>0.05). The gut morphology examination showed that chick origin (chicks that originated from Bio-Mos fed breeders or control fed breeders) did not influence the morphological parameters of the jejunum in the broiler chickens, but addition of Bio-Mos directly to the broiler feed had a significant influence on the gut morphology and played an important role in processes of digestion and absorption, leading to improved performance.Key words: Broiler, mannanoligosaccharides, growth, jejunum, histology

Unraveling the Genotype-Phenotype Relationship in Hypertrophic Cardiomyopathy:Obesity-Related Cardiac Defects as a Major Disease Modifier

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is characterized by asymmetric septal thickening and diastolic dysfunction. More than 1500 mutations in genes encoding sarcomere proteins are associated with HCM. However, the genotype-phenotype relationship in HCM is incompletely understood and involves modification by additional disease hits. Recent cohort studies identify obesity as a major adverse modifier of disease penetrance, severity, and clinical course. In this review, we provide an overview of these clinical findings. Moreover, we explore putative mechanisms underlying obesity-induced sensitization and aggravation of the HCM phenotype. We hypothesize obesity-related stressors to impact on cardiomyocyte structure, metabolism, and homeostasis. These may impair cardiac function by directly acting on the primary mutation-induced myofilament defects and by independently adding to the total cardiac disease burden. Last, we address important clinical and pharmacological implications of the involvement of obesity in HCM disease modification.</p

Photodegradation of methylmercury in stream ecosystems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109966/1/lno20135810013.pd

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Huntington’s disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT). While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecular mechanisms for nonmotor symptoms in HD, such as psychiatric manifestations, remain elusive. Here we have demonstrated that HTT forms a ternary protein complex with the scaffolding protein DISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity. We observed pathological cross-seeding between DISC1 and mutant HTT aggregates in the brains of HD patients as well as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice). In R6/2 mice, consequent reductions in soluble DISC1 led to dysregulation of DISC1-PDE4 complexes, aberrantly increasing the activity of PDE4. Importantly, exogenous expression of a modified DISC1, which binds to PDE4 but not mutant HTT, normalized PDE4 activity and ameliorated anhedonia in the R6/2 mice. We propose that cross-seeding of mutant HTT and DISC1 and the resultant changes in PDE4 activity may underlie the pathology of a specific subset of mental manifestations of HD, which may provide an insight into molecular signaling in mental illness in general

Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury

Many hundreds of thousands of people around the world are living with the long-term consequences of spinal cord injury and they need effective new therapies. Laboratory research in experimental animals has identified a large number of potentially translatable interventions but transition to the clinic is not straightforward. Further evidence of efficacy in more clinically-relevant lesions is required to gain sufficient confidence to commence human clinical trials. Of the many therapeutic candidates currently available, intraspinally applied chondroitinase ABC has particularly well documented efficacy in experimental animals. In this study we measured the effects of this intervention in a double-blinded randomized controlled trial in a cohort of dogs with naturally-occurring severe chronic spinal cord injuries that model the condition in humans. First, we collected baseline data on a series of outcomes: forelimb-hindlimb coordination (the prespecified primary outcome measure), skin sensitivity along the back, somatosensory evoked and transcranial magnetic motor evoked potentials and cystometry in 60 dogs with thoracolumbar lesions. Dogs were then randomized 1:1 to receive intraspinal injections of heat-stabilized, lipid microtube-embedded chondroitinase ABC or sham injections consisting of needle puncture of the skin. Outcome data were measured at 1, 3 and 6 months after intervention; skin sensitivity was also measured 24 h after injection (or sham). Forelimb-hindlimb coordination was affected by neither time nor chondroitinase treatment alone but there was a significant interaction between these variables such that coordination between forelimb and hindlimb stepping improved during the 6-month follow-up period in the chondroitinase-treated animals by a mean of 23%, but did not change in controls. Three dogs (10%) in the chondroitinase group also recovered the ability to ambulate without assistance. Sensitivity of the dorsal skin increased at 24 h after intervention in both groups but subsequently decreased to normal levels. Cystometry identified a non-significant improvement of bladder compliance at 1 month in the chondroitinase-injected dogs but this did not persist. There were no overall differences between groups in detection of sensory evoked potentials. Our results strongly support a beneficial effect of intraspinal injection of chondroitinase ABC on spinal cord function in this highly clinically-relevant model of chronic severe spinal cord injury. There was no evidence of long-term adverse effects associated with this intervention. We therefore conclude that this study provides strong evidence in support of initiation of clinical trials of chondroitinase ABC in humans with chronic spinal cord injury

Deterministically Driven Avalanche Models of Solar Flares

We develop and discuss the properties of a new class of lattice-based avalanche models of solar flares. These models are readily amenable to a relatively unambiguous physical interpretation in terms of slow twisting of a coronal loop. They share similarities with other avalanche models, such as the classical stick--slip self-organized critical model of earthquakes, in that they are driven globally by a fully deterministic energy loading process. The model design leads to a systematic deficit of small scale avalanches. In some portions of model space, mid-size and large avalanching behavior is scale-free, being characterized by event size distributions that have the form of power-laws with index values, which, in some parameter regimes, compare favorably to those inferred from solar EUV and X-ray flare data. For models using conservative or near-conservative redistribution rules, a population of large, quasiperiodic avalanches can also appear. Although without direct counterparts in the observational global statistics of flare energy release, this latter behavior may be relevant to recurrent flaring in individual coronal loops. This class of models could provide a basis for the prediction of large solar flares.Comment: 24 pages, 11 figures, 2 tables, accepted for publication in Solar Physic

Anti-inflammatory phytotherapeutics: a valuable alternative to NSAID treatment in horses?

ABSTRACT In equine practice, phytotherapy is meeting the increasing demand of horse owners for &quot;natural&quot;, safe treatment methods. Long-term use of NSAIDs can cause severe adverse effects, hence the growing popularity of anti-inflammatory phytotherapeutics. At the current time, several different herbal mixes are being commercialized, which makes it difficult for horse owners and veterinarians alike to make a well-founded choice. Harpagophytum procumbens (devil&apos;s claw), Salix spp. (willow) and Ribes nigrum (blackcurrant), three plants that are often used in these mixes, have been evaluated both in vitro and in vivo. Based on published studies and the evaluation of these studies, for example by the Cochrane Collaboration, there seems to be some evidence for Harpagophytum procumbens and Salix spp. having a stronger analgesic and anti-inflammatory effect than placebos in humans. In horses, however, only one limited clinical study on Harpagophytum has been performed up until now, while no studies were found on the use of Salix in horses. More research is needed before any claims concerning efficacy or safety can be made regarding the use of these plants in treating horses. It has also been claimed that Ribes nigrum leaves have an anti-inflammatory effect, though this has not yet been clinically proven either in humans or in horses. Although veterinary phytotherapy is as old as animal husbandry itself, little scientific proof can be found regarding its uses. More research is needed before phytotherapy can be advertised as a valuable and safe alternative to the more conventional treatment protocols. SAMENVATTING In de paardengeneeskunde is fytotherapie een antwoord op de toenemende vraag van eigenaren naar &quot;natuurlijke&quot;, veilige behandelmethoden. Het langdurig gebruik van NSAID&apos;s kan ernstige bijwerkingen geven, vandaar de groeiende populariteit van ontstekingsremmende fytotherapeutica. Momenteel zijn er meerdere kruidenpreparaten commercieel beschikbaar maar het is moeilijk voor de paardeneigenaar en de dierenarts om hier een verantwoorde keuze uit te maken. Harpagophytum procumbens (duivelsklauw), Salix spp. (wilg) en Ribes nigrum (zwarte bes of cassisbes), drie planten die veel gebruikt worden in de commerciële preparaten, werden zowel in vitro als in vivo geëvalueerd. Op basis van gepubliceerde studies en de beoordeling van deze studies door onder andere de Cochrane Collaboration zijn er aanwijzingen dat Harpagophytum procumbens en Salix spp. bij de mens een groter analgetisch en ontstekingsremmend effect hebben dan een placebo. Bij paarden is er echter slechts één beperkte klinische studie met Harpagophytum uitgevoerd, en het effect van Salix werd nog nooit onderzocht. Om de werkzaamheid en veiligheid van deze planten bij het paard te kunnen beoordelen, dient er meer onderzoek verricht te worden. De bladeren van Ribes nigrum zouden ook een ontstekingsremmende werking hebben, maar dit is momenteel noch bij de mens, noch bij het paard klinisch aangetoond. Hoewel de veterinaire fytotherapie al even lang bestaat als de dierhouderij, is er weinig wetenschappelijk bewijs omtrent een efficiënte werking ervan. Vooraleer men de fytotherapie kan aanraden als een waardevol en veilig alternatief voor de conventionele behandelmethoden, is er duidelijk nog meer onderzoek nodig

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy

Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.

STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression