Snake fungal disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been ...suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To determine the pharmacodynamics and pharmacokinetics of rivaroxaban (RVX), in healthy cats and to evaluate the clinicopathologic effects of various plasma RVX concentrations within ...target therapeutic ranges established for people.
Design
Prospective randomized cross‐over study performed between July 2013 and November 2014.
Setting
Veterinary university teaching hospital.
Animals
Six healthy adult domestic shorthair cats (3 males, 3 females).
Interventions
Cats were treated with oral RVX at single, fixed doses (1.25, 2.5, 5 mg PO), q 12 h for 3 days (1.25 mg); q 24 h for 7 days (2.5 mg); and q 24 h for 28 days (1.25 mg). Blood samples were collected for complete blood count, blood chemistry, and RVX anticoagulant activity based on prolongation of dilute prothrombin time, activated partial thromboplastin time (aPTT), activated Factor X (FXa) inhibition (anti‐Xa activity aXa) and high‐pressure liquid chromatography tandem mass spectrometry determination of drug concentration.
Measurements and Main Results
Treated cats had no signs of hemorrhage or clinicopathologic off‐target adverse effects. There were dose‐dependent prolongations of coagulation times and increase in aXa, with peak effect at 3 hours postadministration. There was a direct correlation between plasma RVX concentration and dilute prothrombin time and aXa. Coagulation parameters returned to baseline by 24 hours after the last dose.
Conclusions
Oral RVX was well tolerated by healthy cats with predictable pharmacokinetics and anticoagulant effects. Clinical studies of RVX are warranted in cats with heart disease.
Snake fungal disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been ...suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The problem of providing the animal products needed for our increasing world population is currently the subject of numerous scientific investiga- tions. This problem is being met by research ...developments that are increas- ing the feed efficiency of animal production and enabling animals to draw more on food resources not suitable for man's direct use. The dietary value of animal products lies mainly in the high quality proteins, minerals, and vitamins supplied and not in their caloric contribution. Caloric intake among the world population is adequate as seventy percent of the total food of the majority of the world population is cereals. Animal products are important to man's mutrition and health as taey supplement man's other sources of food.When evaluating the efficiency of an animal one must consider the type of feed it consumes. Ruminants are inefficient nutrient producers on a gross energy intake basis, but man cannot use the roughage feeds they consume nor utilize nonprotein nitrogen compounds to replace part of the natural protein in the diet. The unique and complex microbial fermentation proceвлев occurring in the rumen thus enable the ruminant to be competitive.
Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2000.
Includes bibliographical references (p. 87-89).
by Edward Loper.
M.Eng.
Alkyne-containing natural products have been identified from plants, insects, algae, fungi, and bacteria. This class of natural products has been characterized as having a variety of biological ...activities. Polyynes are a subclass of acetylenic natural products that contain conjugated alkynes and are underrepresented in natural product databases due to the fact that they decompose during purification. Here we report a workflow that utilizes alkyne azide cycloaddition (AAC) reactions followed by LC-MS/MS analysis to identify acetylenic natural products. In this report, we demonstrate that alkyne azide cycloaddition reactions with p-bromobenzyl azide result in p-bromobenzyl-substituted triazole products that fragment to a common brominated tropylium ion. We were able to identify a synthetic alkyne spiked into the extract of Anabaena sp. PCC 7120 at a concentration of 10 μg/mL after optimization of MS/MS conditions. We then successfully identified the known natural product fischerellin A in the extract of Fischerella muscicola PCC 9339. Lastly, we identified the recently identified natural products protegenins A and C from Pseudomonas protegens Pf-5 through a combination of genome mining and RuAAC reactions. This is the first report of RuAAC reactions to detect acetylenic natural products. We also compare CuAAC and RuAAC reactions and find that CuAAC reactions produce fewer byproducts compared to RuAAC but is limited to terminal-alkyne-containing compounds. In contrast, RuAAC is capable of identification of both terminal and internal acetylenic natural products, but byproducts need to be eliminated from analysis by creation of an exclusion list. We believe that both CuAAC and RuAAC reactions coupled to LC-MS/MS represent a method for the untargeted identification of acetylenic natural products, but each method has strengths and weaknesses.
When space became available, the farm office moved into Tassafaronga Village’s renovated factory building – extending the farm’s helping hand by offering a quiet working space for community members. ...Creating connection in new housing In our book “9 Ways to Make Housing for People,” we outline the core principles and strategies that help communities achieve real quality and value in new housing. Placing the community room near the front door draws residents and visitors into activities; connecting the laundry room with a play area allows parents to get tasks done while kids run and climb.
The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) ...during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferons. Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon- promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Depletion of NLRX1 with small interference RNA promotes virus-induced type I interferon production and decreases viral replication. This work identifies NLRX1 as a check against mitochondrial antiviral responses and represents an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti-pathogen signalling. This represents a conceptual advance, in that NLRX1 is a modulator of pathogen-associated molecular pattern receptors rather than a receptor, and identifies a key therapeutic target for enhancing antiviral responses.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
The unicellular alga Chlamydomonas reinhardtii and the bacterium Pseudomonas protegens serve as a model to study the interactions between photosynthetic and heterotrophic microorganisms. P. ...protegens secretes the cyclic lipopeptide orfamide A that interferes with cytosolic Ca2+ homeostasis in C. reinhardtii resulting in deflagellation of the algal cells. Here, we studied the roles of additional secondary metabolites secreted by P. protegens using individual compounds and co‐cultivation of algae with bacterial mutants. Rhizoxin S2, pyrrolnitrin, pyoluteorin, 2,4‐diacetylphloroglucinol (DAPG) and orfamide A all induce changes in cell morphology and inhibit the growth of C. reinhardtii. Rhizoxin S2 exerts the strongest growth inhibition, and its action depends on the spatial structure of the environment (agar versus liquid culture). Algal motility is unaffected by rhizoxin S2 and is most potently inhibited by orfamide A (IC50 = 4.1 μM). Pyrrolnitrin and pyoluteorin both interfere with algal cytosolic Ca2+ homeostasis and motility whereas high concentrations of DAPG immobilize C. reinhardtii without deflagellation or disturbance of Ca2+ homeostasis. Co‐cultivation with a regulatory mutant of bacterial secondary metabolism (ΔgacA) promotes algal growth under spatially structured conditions. Our results reveal how a single soil bacterium uses an arsenal of secreted antialgal compounds with complementary and partially overlapping activities.
Forecasting of solar flares remains a challenge due to the limited understanding of the underlying physical processes of these events, in particular magnetic reconnection. Studies have indicated that ...changes to the photospheric magnetic fields associated with magnetic reconnection – particularly in relation to the field helicity – occur during solar flare events. This study utilized data from the Solar Dynamics Observatory (SDO) Helioseismic and Magnetic Imager (HMI) and SpaceWeather HMI Active Region Patches (SHARPs) to analyze full vector-field component data of the photospheric magnetic field during solar flare events within a near decade long HMI dataset. Analysis of the data was used to identify and compare the trends of differing flare classes for varying time intervals leading up to an event, as well as the trends of flares that occur with and without a precursor flare, in order to discern signatures of the physical mechanisms involved. The data suggests that active regions that produce flares with precursors are continuing to evolve and appreciably more complex than those that produce a flare without a precursor. Additionally, precursor flares were found to enhance the shear across an active region, helping set up the conditions necessary for a larger solar flare to occur. Ultimately none of the SHARP parameters showed a distinct signature of magnetic reconnection.
•Differences in active region magnetic parameters between flares with and without a precursor are greatest for X-class flares.•The effect of precursors in adjusting the magnetic conditions of an active region is most significant within a 6-hour period.•ARs with X-class flares with no precursor have reached max growth; ARs with X-class flares with a precursor are still growing.•Precursors enhance the shear over an AR, helping set up conditions for magnetic reconnection necessary for a larger flare.
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