A field study of management stress in reindeer (Rangifer tarandus L)

The impact of stress was studied in semidomesticated reindeer subjected to various herding and handling methods. In herded and handled animals, stress lesions were found, such as abomasal haemorrhage, muscular and myocardial degeneration and marked changes in blood constituents. The degree of change was dependent of the magnitude of stress the animal had been exposed to. Manual handling and restraint was found to be one of the major stress factors. There were evident indications of a cumulative effect of repeated stress events. The use of motor vehicles (helicopter and snow-scooter), for herding and transporting the animals, was found to be an important stress factor. It is concluded that various herding and handling methods studied in the present investigation led to varying degrees of deleterious effects on the health of the animals and a poorer meatquality from slaughtered animals. Hence herding should be undertaken as carefully as possible, the time taken for manual handling should be minimized, and the corrals be so constructed as to cause a minimum of disturbance, capture and restraint. Transportation should be undertaken very cautiously with as little manual handling as possible during loading and unloading. To obtain a good meat quality, animals to be slaughtered should be subjected to a minimum of handling, i.e. slaughter should take place as quickly as possible. Transportation of live animals to slaughterhouses and the keeping of animals in corrals, pens or crates whilst awaiting slaughter will result in a lowered meat quality and should therefore be avoided.En fåltstudie av stress hos ren i samband med olika hanteringsformer.Abstract in Swedish / Sammanfatning: Betydelsen av stress hos ren studerades i hjordar i vilka olika typer av samlings- och hanteringsmetoder anvandes. I samtliga hjordar som utsatts for olika former av drivning forelag hos slaktdjur skador betingade av stress i form av magblodningar, muskelsonderfall och forandringar i blodbilden. De funna skadorna och forandringarna var beroende av den grad av stress som djuren utsatts for. Manuell hantering och inskrankning av djurens rorelsefrihet befanns vara en av de huvudsakliga stressfaktorerna. Det forelag åvenledes en stark indikation på en kumulativ effekt av upprepad stress. Anvandning av motorfordon (helikopter, snoskoter) vid drivning samt vågtransport av levande djur befanns vara betydande stressfaktorer. Det kan fastslås att de olika hanteringsformerna inneburit olika grader av stress. Graden av stresspåverkan innebår olika grader av negativa effekter dels allmånt for djurens hålsotillstånd dels for en forsåmrad kottkvalitet. Sålunda bor drivningar foretagas så forsiktigt som mojligt och tiden for manuell hantering goras så kort som mpjlig. Dårtill bor gårdor konstrueras så att yttre storning, manuell hantering och begrånsning av djurens rorelsefrihet minimeras. Transporter bor genomforas med forsiktighet och med undvikande av manuell hantering vid lastning och lossning. Slakt bor foretagas omedelbart, dvs vid gårdan. Transport av levande djur, samt hållandet av djur i gårdor eller fillor i vantan på slakt innebår att kottkvaliteten forsåmras och bor således undvikas.Kenttâtutkimus porojen stressistâ erilaisten kâsittelymuotojen yhteydessà.Abstract in Finnish / Yhteenveto: Stressin merkitystâ poroissa tutkitaan laumoissa, joissa kàytetààn erilaisia kokoamis - ja kàsittelymenetelmià. Kaikissa laumoissa, jotka olivat joutuneet alttiiksi erilaisille ajomuodoille, oli teuraselàimissâ stressin aiheuttamia vammoja mahaverenvuotojen, lihasrappeutumien ja verikuvan muutosten muodossa. Lôydetyt vammat ja muutokset olivat stressin aiheuttamat siina suhteessa kuin elaimet olivat siihen joutuneet. Kàsin pitely ja elàinten liikuntavapauden rajoittuminen havaittiin olevan yksi pààsiallisista stressintekijôistà. Oli esillà myôs voimakas osoitus kasvavan vaikutuksen toistuvasta stressistâ. Moottoriajoneuvojen (helikopteri, moottori-kelkka) kàyttô ajossa sekà elàvien elàinten tiekuljetus nayttivàt olevan merkittàvià stressitekijôità. Voidaan todeta, ettà erilaiset kasittelymuodot ovat aiheuttaneet stressin erilaisia asteita. Stressin vaikutuksen taso aiheutti eri asteisia negatiivisia vaikutuksia osittain huonontuneeseen lihan laatuun. Nainollen pitàà ajot suorittaa niin varovaisesti kuin mahdollista ja aika kàsin pitelyyn tehtàvà niin lyhyeksi kuin mahdollista. Sen lisàksi pitàà aidât rakentaa niin, ettà ulkoista hàirintàà, kàsin pitelyà ja elàinten liikuntavapauden rajoitusta vàhennetààn. Kuljetukset pitàà suorittaa varovaisuudella ja koettaa vàlttàà kàsin pitelyà kuormauksessa ja purkauksessa. Teurastaminen pitàà suorittaa vâlittômàsti, toisin sanoen aidan luona. Elàvien elàinten kuljetus, sekà elàinten pitàminen aitauksissa tai tarhoissa teurastamista odotellessa aiheuttaa lihalaadun huonontumiseen ja pitàà nàin ollen vàlttàà

Fiber Mediated Receptor Masking in Non-Infected Bystander Cells Restricts Adenovirus Cell Killing Effect but Promotes Adenovirus Host Co-Existence

The basic concept of conditionally replicating adenoviruses (CRAD) as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI), and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses

GABA-A Channel Subunit Expression in Human Glioma Correlates with Tumor Histology and Clinical Outcome

GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the CNS and is present in high concentrations in presynaptic terminals of neuronal cells. More recently, GABA has been ascribed a more widespread role in the control of cell proliferation during development where low concentrations of extrasynaptic GABA induce a tonic activation of GABA receptors. The GABA-A receptor consists of a ligand-gated chloride channel, formed by five subunits that are selected from 19 different subunit isoforms. The functional and pharmacological properties of the GABA-A channels are dictated by their subunit composition. Here we used qRT-PCR to compare mRNA levels of all 19 GABA-A channel subunits in samples of human glioma (n = 29) and peri-tumoral tissue (n = 5). All subunits except the ρ1 and ρ3 subunit were consistently detected. Lowest mRNA levels were found in glioblastoma compared to gliomas of lower malignancy, except for the θ subunit. The expression and cellular distribution of the α1, γ1, ρ2 and θ subunit proteins was investigated by immunohistochemistry on tissue microarrays containing 87 gliomas grade II. We found a strong co-expression of ρ2 and θ subunits in both astrocytomas (r = 0.86, p<0.0001) and oligodendroglial tumors (r = 0.66, p<0.0001). Kaplan-Meier analysis and Cox proportional hazards modeling to estimate the impact of GABA-A channel subunit expression on survival identified the ρ2 subunit (p = 0.043) but not the θ subunit (p = 0.64) as an independent predictor of improved survival in astrocytomas, together with established prognostic factors. Our data give support for the presence of distinct GABA-A channel subtypes in gliomas and provide the first link between specific composition of the A-channel and patient survival

Crystal Structure of the Heteromolecular Chaperone, AscE-AscG, from the Type III Secretion System in Aeromonas hydrophila

10.1371/journal.pone.0019208PLoS ONE64

GABA Maintains the Proliferation of Progenitors in the Developing Chick Ciliary Marginal Zone and Non-Pigmented Ciliary Epithelium

GABA is more than the main inhibitory neurotransmitter found in the adult CNS. Several studies have shown that GABA regulates the proliferation of progenitor and stem cells. This work examined the effects of the GABAA receptor system on the proliferation of retinal progenitors and non-pigmented ciliary epithelial (NPE) cells. qRT-PCR and whole-cell patch-clamp electrophysiology were used to characterize the GABAA receptor system. To quantify the effects on proliferation by GABAA receptor agonists and antagonists, incorporation of thymidine analogues was used. The results showed that the NPE cells express functional extrasynaptic GABAA receptors with tonic properties and that low concentration of GABA is required for a baseline level of proliferation. Antagonists of the GABAA receptors decreased the proliferation of dissociated E12 NPE cells. Bicuculline also had effects on progenitor cell proliferation in intact E8 and E12 developing retina. The NPE cells had low levels of the Cl–transporter KCC2 compared to the mature retina, suggesting a depolarising role for the GABAA receptors. Treatment with KCl, which is known to depolarise membranes, prevented some of the decreased proliferation caused by inhibition of the GABAA receptors. This supported the depolarising role for the GABAA receptors. Inhibition of L-type voltage-gated Ca2+ channels (VGCCs) reduced the proliferation in the same way as inhibition of the GABAA receptors. Inhibition of the channels increased the expression of the cyclin-dependent kinase inhibitor p27KIP1, along with the reduced proliferation. These results are consistent with that when the membrane potential indirectly regulates cell proliferation with hyperpolarisation of the membrane potential resulting in decreased cell division. The increased expression of p27KIP1 after inhibition of either the GABAA receptors or the L-type VGCCs suggests a link between the GABAA receptors, membrane potential, and intracellular Ca2+ in regulating the cell cycle

Evolution of an endofungal Lifestyle: Deductions from the Burkholderia rhizoxinica Genome

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia rhizoxinica </it>is an intracellular symbiont of the phytopathogenic zygomycete <it>Rhizopus microsporus</it>, the causative agent of rice seedling blight. The endosymbiont produces the antimitotic macrolide rhizoxin for its host. It is vertically transmitted within vegetative spores and is essential for spore formation of the fungus. To shed light on the evolution and genetic potential of this model organism, we analysed the whole genome of <it>B. rhizoxinica </it>HKI 0454 - a type strain of endofungal <it>Burkholderia </it>species.</p> <p>Results</p> <p>The genome consists of a structurally conserved chromosome and two plasmids. Compared to free-living <it>Burkholderia </it>species, the genome is smaller in size and harbors less transcriptional regulator genes. Instead, we observed accumulation of transposons over the genome. Prediction of primary metabolic pathways and transporters suggests that endosymbionts consume host metabolites like citrate, but might deliver some amino acids and cofactors to the host. The rhizoxin biosynthesis gene cluster shows evolutionary traces of horizontal gene transfer. Furthermore, we analysed gene clusters coding for nonribosomal peptide synthetases (NRPS). Notably, <it>B. rhizoxinica </it>lacks common genes which are dedicated to quorum sensing systems, but is equipped with a large number of virulence-related factors and putative type III effectors.</p> <p>Conclusions</p> <p><it>B. rhizoxinica </it>is the first endofungal bacterium, whose genome has been sequenced. Here, we present models of evolution, metabolism and tools for host-symbiont interaction of the endofungal bacterium deduced from whole genome analyses. Genome size and structure suggest that <it>B. rhizoxinica </it>is in an early phase of adaptation to the intracellular lifestyle (genome in transition). By analysis of tranporters and metabolic pathways we predict how metabolites might be exchanged between the symbiont and its host. Gene clusters for biosynthesis of secondary metabolites represent novel targets for genomic mining of cryptic natural products. <it>In silico </it>analyses of virulence-associated genes, secreted proteins and effectors might inspire future studies on molecular mechanisms underlying bacterial-fungal interaction.</p

Timing is everything: the regulation of type III secretion

Type Three Secretion Systems (T3SSs) are essential virulence determinants of many Gram-negative bacteria. The T3SS is an injection device that can transfer bacterial virulence proteins directly into host cells. The apparatus is made up of a basal body that spans both bacterial membranes and an extracellular needle that possesses a channel that is thought to act as a conduit for protein secretion. Contact with a host-cell membrane triggers the insertion of a pore into the target membrane, and effectors are translocated through this pore into the host cell. To assemble a functional T3SS, specific substrates must be targeted to the apparatus in the correct order. Recently, there have been many developments in our structural and functional understanding of the proteins involved in the regulation of secretion. Here we review the current understanding of protein components of the system thought to be involved in switching between different stages of secretion