Improving the clinical efficiency of T2 mapping of ligament integrity

Current MR methods use T₂^? relaxation time as a surrogate measure of ligament strength. Currently, a multi-echo voxel-wise least squares fit is the gold standard to create T₂^? maps; however, the post-processing is time-intensive and serves as a stopgap for clinical use. The study objective was to determine if an alternative method could improve post-processing time without sacrificing fidelity of T₂^? values for eventual translational use in the clinic. Using a 6 echo FLASH sequence, three different methods were used to determine intact posterior cruciate ligament (PCL) median T₂^? Two of these methods utilized a voxel-wise method to establish T₂^? maps: (1) a current “gold standard” method using a voxel-wise 6 echo least-squares fit (6LS) and (2) a voxel-wise 2 echo point T₂^? determination (2MM). The third method used median ligament signal intensity and a single nonlinear least-squares fit (6LS_ROI) instead of a voxel-wise basis. The resulting median T₂^? values of the PCL and computational time were compared. The median T₂^? values were 42% higher using the 2MM compared to the 6LS method (p<0.0001). However, a strong correlation was found for the median T₂^? values between the 2MM and 6LS methods (R²=0.80). The median T₂^? values were not significantly different between the 6LS and 6LS_ROI methods (p=0.519). Using the 2MM (which provides a regional map) and the 6LS_ROI (which efficiently provides the median T₂^? value) methods in tandem would take only minutes of post-processing computational time compared to the 6LS method (~540 min), and hence would facilitate clinical application of T₂^? maps to predict ligament structural properties as a patient outcome measure.     

Wavelet-synchrony of Brain Evoked Responses during Listening to Naturalistic Stimuli in the Prognosis of Consciousness Recovery (Study 1: Wavelet-synchrony during Listening to Instrumental Music)

The features and prognostic value of wavelet-synchrony of evoked responses during the listening to realistic stimuli (music) were revealed in the study. Musical passages were selected according the patients’ preferences by their relations consultation. Wavelet-connections were calculated for each melody in the range from 0 to 1000 ms from stimuli. Total 22 examinees in 12 patients being in unconsciousness state were carried out. Resting state values of wavelet-connectivity were poorer in vegetative patients in comparison to healthy subjects regardless of consciousness recovery degree in future while wavelet-connections in mutism were higher in comparison to healthy subjects. Absolute value of wavelet-synchrony was lower than in norm. In patients with compete consciousness recovery in the future the maximal values of wavelet-synchrony were revealed in the temporal-occipital area while in patients who in the future have been revealed in the lesser degree the maximal values of wavelet-synchrony are shown in frontal-central areas. In chronic unconsciousness patients during the listening to instrumental music the maximal wavelet-connections values were determined in the right frontal area.     

Infiltration of a facultative ant–plant mutualism by the introduced Argentine ant: effects on mutualist diversity and mutualism benefits

1. Ant–plant mutualisms have been the focus of considerable empirical research, but few studies have investigated how introduced ants affect these interactions. Using 2 years of survey data, this study examines how the introduced Argentine ant [Linepithema humile (Mayr)] differs from native ants with respect to its ability to protect the extrafloral nectary‐bearing coast barrel cactus (Ferocactus viridescens) in Southern California. 2. Eighteen native ant species visited cacti in uninvaded areas, but cacti in invaded areas were primarily visited by the Argentine ant. The main herbivore of the coast barrel cactus present at the study sites is a leaf‐footed bug (Narnia wilsoni). 3. Herbivore presence (the fraction of surveys in which leaf‐footed bugs were present on individual cacti) was negatively related to ant presence (the fraction of surveys in which ants were present on individual cacti). Compared with cacti in uninvaded areas, those in invaded areas were less likely to have herbivores and when they did had them less often. 4. Seed mass was negatively related to herbivore presence, and this relationship did not differ for cacti in invaded areas versus those in uninvaded areas. 5. Although the Argentine ant might provide superior protection from herbivores, invasion‐induced reductions in ant mutualist diversity could potentially compromise plant reproduction. The cumulative number of ant species on individual cacti over time was lower in invaded areas and was associated with a shortened seasonal duration of ant protection and reduced seed mass. These results support the hypothesis that multiple partners may enhance mutualism benefits.     

Diminished Reovirus Capsid Stability Alters Disease Pathogenesis and Littermate Transmission

Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein. However, the contribution of capsid stability to reovirus-induced disease is unknown. In this study, we found that mice inoculated intramuscularly with a serotype 3 reovirus containing σ3-Y354H, a mutation that reduces viral capsid stability, succumbed at a higher rate than those infected with wild-type virus. At early times after inoculation, σ3-Y354H virus reached higher titers than wild-type virus at several sites within the host. Animals inoculated perorally with a serotype 1 reassortant reovirus containing σ3-Y354H developed exaggerated myocarditis accompanied by elaboration of pro-inflammatory cytokines. Surprisingly, unchallenged littermates of mice infected with σ3-Y354H virus displayed higher titers in the intestine, heart, and brain than littermates of mice inoculated with wild-type virus. Together, these findings suggest that diminished capsid stability enhances reovirus replication, dissemination, lethality, and host-to-host spread, establishing a new virulence determinant for nonenveloped viruses.     

Suppression of dexamethasone-stimulated DNA synthesis in an oncogene construct containing rat cell line by a DNA site-oriented ligand of poly-ADP-ribose polymerase: 6-amino-1,2-benzopyrone

The cellular inhibitory effects of 6-amino-1,2-benzopyrone (6-ABP), a DNA site-specific ligand of adenosine diphosphoribosyl transferase (ADPRT), were determined in a dexamethasone-sensitive EJ-ras gene construct containing cell line (14C cells). Dexamethasone in vitro transforms these cells to a tumorigenic phenotype and also stimulates cell replication. At a non-toxic concentrations (0.2 mM) 6-ABP treatment of intact cells for 4 days inhibits the dexamethasone-stimulated increment of cellular DNA content, depresses replicative DNA synthesis as assayed by thymidine incorporation to the level of cells that were not exposed to dexamethasone, and in permeabilized cells reduces the dexamethasone-stimulated increase of deoxyribonucleotide incorporation into DNA to the level of untreated cells. In situ pulse labeling of cells pretreated with 6-ABP indicated an inhibition of DNA synthesis at a stage prior to the formation of the 10-kb intermediate species. The drug had no direct effect on cellular DNA polymerases as tested in vitro, and the inhibition of DNA synthesis in permeabilized cells following drug treatment for 4 days was abolished by externally added DNA templates. Neither dexamethasone nor the drug influenced the cellular quantity of ADPRT molecules, tested immunochemically.     

Identification of a 42 kDa protein as a substrate of protein phosphatase 1 in cilia from Paramecium.

Okadaic acid, a specific inhibitor of protein phosphatase 1 in Paramecium causes sustained backward swimming in response to depolarising stimuli (S. Klumpp et al. (1990) EMBO J. 9, 685). Here, we employ okadaic acid, tautomycin, microcystin LR and inhibitor 1 as phosphatase inhibitors to identify a 42 kDa protein in the excitable ciliary membrane that is dephosphorylated by protein phosphatase 1. Identification of the 42 kDa protein was facilitated by the finding that the protein kinase responsible for its phosphorylation uses Ca-ATP as a substrate just as effectively as Mg-ATP. Notably, dephosphorylation of the 42 kDa protein is specifically inhibited by cyclic AMP; cyclic GMP has no effect.     

Pretreatment with drug-specific antibody reduces desipramine cardiotoxicity in rats

The effect of a drug-specific antibody on desipramine (DMI) cardiotoxicity was studied in rats. Animals were pretreated i.v. with 4.2 g/kg of a monoclonal antibody (anti-TCA) followed by DMI HCl 30 mg/kg i.p. (molar ratio of anti-TCA binding sites to DMI = 0.56). Peak QRS complex prolongation was substantially lower after pretreatment with anti-TCA than after control antibody (70 +/- 14 v. 21 +/- 4%, p less than 0.001). Time to peak toxicity was the same in both groups. Binding of DMI by anti-TCA was demonstrated by a higher serum total DMI concentration and increased DMI binding in serum after anti-TCA compared to controls. The DMI concentration in anti-TCA treated animals was lower in some organs (brain, lung, liver, spleen), but not in others (heart, muscle, kidney, fat). The calculated fraction of the DMI dose bound by anti-TCA was 19.9%. The steepness of the DMI dose-response curve was examined by administering DMI alone (without antibody) at various doses to rats. Compared to 30 mg/kg DMI, a dose reduction of 30-50% was needed to reduce QRS duration to the same extent as anti-TCA pretreatment. We conclude that DMI cardiotoxicity was markedly reduced by the binding of a relative small fraction of the DMI body burden to anti-TCA. This disproportionate effect of DMI binding was not due to the steepness of the DMI dose-response curve, nor to slowing of the rate of DMI distribution to tissues.     

Phosphatases modulate transmission and serotonin facilitation at synapses: Studies with the inhibitor okadaic acid

We examined the role of phosphatases in synaptic transmission using the permeant phosphatase inhibitor okadaic acid (OA). In the crayfish neuromuscular junction (NMJ), postsynaptic effects including increases in input resistance occurred at doses greater than 5 μM OA. At lower doses (0.5–5 μM) the effects were solely presynaptic and transmitter release increased over three-fold despite small reductions in amplitude and duration of presynaptic action potentials. Potentiating effects of serotonin on transmitter release, Which depend on phosphorylation, were increased by OA. Frequency facilitation was reduced but its decay was not affected. In frog NMJs, OA increased spontaneous and evoked release two-fold through presynaptic mechanisms. An inactive analog of OA, OA tetra-acetate, had no effect on transmitter release at frog and crayfish NMJ. Therefore, phosphatases have a strong modulating influence on synaptic transmission.     

Chemical and microbiological solubilization of silicates

The solubilization of silicates was investigated using kaolin and quartz sand as model substances. The mineral solubilization was studied in the concentration of solubilized Si and Al. The chemical leaching of the silicates was carried out using inorganic and organic acids as well as sodium hydroxide. The process was more effective in the alkine than in the acid pH range. In the acid medium, oxalic acid showed maximum acidity and a tendency to form complex structures, especially with aluminium, and was most effective in leaching. The microbiological influence on solubilization reactions was tested using a number of microorganisms among them acid, alkali and slime-forming species. The highest leaching activity was observed in the case of Thiobacillus thiooxidans, whereas the heterotrophic microorganisms (among them Bacillus mucilaginosus) did not exercise a sollubilizing effect on the silicates. X-ray phase analysis of leached kaolin samples did not show any differences from the non-leached mineral.