68 research outputs found
Peste des petits ruminants virus tissue tropism and pathogenesis in sheep and goats following experimental infection
Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic
losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East
and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however
recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models.
This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using
a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical
signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV
was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs
were the predominant sites of virus replication. The results presented in this study provide models for the comparative
evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the
establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host
interactions.A Canadian International Food Security Research Fund (CIFSRF) grant (no. 106930: Livestock vaccines against viral diseases
for sub-Saharan Africa) by the Canadian International Development Research Centre (IDRC) and Canadian International Development Agency (CIDA).http://www.plosone.orgam201
In Vitro and In Vivo Characterization of the Alkaloid Nuciferine
RationaleThe sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.MethodsNuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.ResultsNuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.ConclusionsThe molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions
Mating success of male hermit crabs in shell generalist and shell specialist species
The reproductive behavior of two species of diogenid hermit crabs was studied in Hawaii. In the shell generalist, Clibanarius zebra , male reproductive success varied little with size, although the largest males were less successful in obtaining copulations than were medium-large males. Male and female size were positively correlated, in successful pairs, thus larger males had the potential to fertilize more eggs when they were successful in obtaining a copulation. Female fecundity in C. zebra was not affected by species of gastropod shell inhabited once female size was taken into account. Male copulatory success was very strongly influenced by the species of gastropod shell inhabited. Males in Trochus or Nerita shells had greatly reduced reproductive success compared to males in Turbo or Nassarius shells. This result was due both to (1) males in Trochus especially dropping and otherwise poorly handling females during precopulatory behavior and (2) females not responding to precopulatory behavior patterns executed by males in Trochus and Nerita . Transferring males from âgoodâ to âbadâ shapes of shells and vice versa showed that male success was a function of shell type inhabited and not some correlated feature of the crabs. In the shell specialist, Calcinus seurati , which is found primarily in Nerita shells as an adult, males in Nerita shells were quite successful in obtaining copulations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46893/1/265_2004_Article_BF00302928.pd
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017
Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri
The Left-Right Coordinator: The Role of Vg1 in Organizing Left-Right Axis Formation
AbstractThe asymmetries of internal organs are consistently oriented along the left-right axis in all vertebrates, and perturbations of left-right orientation lead to significant congenital disease. We propose a model in which a âleft-right coordinatorâ interacts with the Spemann organizer to coordinate the evolutionarily conserved three-dimensional asymmetries in the embryo. The Vg1 cell-signaling pathway plays a central role in left-right coordinator function. Antagonists of Vg1 alter left-right development; antagonists of other members of the TGFÎČ family do not. Cell-lineage directed expression of Vg1 protein can fully invert the left-right axis (situs inversus), can randomize left-right asymmetries, or can ârescueâ a perturbed left-right axis in conjoined twins to normal orientation (situs solitus), indicating that Vg1 can mimic left-right coordinator activity. These are the first molecular manipulations in any vertebrate by which the left-right axis can be reliably controlled
Emergent Coordination of the CHKB and CPT1B Genes in Eutherian Mammals: Implications for the Origin of Brown Adipose Tissue
Mitochondrial fatty acid oxidation (FAO) contributes to the proton motive force that drives ATP synthesis in many mammalian tissues. In eutherian (placental) mammals, brown adipose tissue (BAT) can also dissipate this proton gradient through uncoupling protein 1 (UCP1) to generate heat, but the evolutionary events underlying the emergence of BAT are unknown. An essential step in FAO is the transport of cytoplasmic long chain acyl-coenzyme A (acyl-CoA) into the mitochondrial matrix, which requires the action of carnitine palmitoyltransferase 1B (CPT1B) in striated muscle and BAT. In eutherians, the CPT1B gene is closely linked to the choline kinase beta (CHKB) gene, which is transcribed from the same DNA strand and terminates just upstream of CPT1B. CHKB is a rate-limiting enzyme in the synthesis of phosphatidylcholine (PC), a predominant mitochondrial membrane phospholipid, suggesting that the coordinated expression of CHKB and CPT1B may cooperatively enhance mitochondrial FAO. The present findings show that transcription of the eutherian CHKB and CPT1B genes is linked within a unitary epigenetic domain targeted to the CHKB gene, and that that this regulatory linkage appears to have resulted from an intergenic deletion in eutherians that significantly altered the distribution of CHKB and CPT1B expression. Informed by the timing of this event relative to the emergence of BAT, the phylogeny of CHKB-CPT1B synteny, and the insufficiency of UCP1 to account for eutherian BAT, these data support a mechanism for the emergence of BAT based on the acquisition of a novel capacity for adipocyte FAO in a background of extant UCP1
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