Tricyclic Guanidine Alkaloids from the Marine Sponge Acanthella cavernosa that Stabilize the Tumor Suppressor PDCD4

A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC₅₀ values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.     

Death from anthropogenic causes is partially compensatory in recovering wolf populations

There is substantial interest in how mortality rates affect animal populations, but mechanisms explaining when and under what circumstances particular causes of death incur demographic responses are far from clear. In theory, small or expanding populations should experience additive mortality from anthropogenic causes of death, but whether such effects are homogenous across a population or expressed only in certain high-risk individuals is open for debate. We used competing risks models to analyze mortality patterns among radio-collared wolves (Canis lupus, n = 711) from three populations in northwestern United States (1982-2004), and evaluated the degree to which anthropogenic mortality was additive vs. compensatory to natural demographic processes. Almost 80% (n = 320) of wolves dying of known fates were killed by anthropogenic causes (legal control, illegal killing, harvest in Canada, vehicle collision), and additive effects of anthropogenic mortality were most pronounced in northwestern Montana where wolf exposure to humans and livestock was high compared to either the Greater Yellowstone Area or central Idaho, where anthropogenic risk was lower. In contrast, risk from natural hazards was lower in northwestern Montana than in the other areas, implying some degree of compensatory mortality from anthropogenic risk. Animals recruited to the study following human-wolf conflict had markedly higher anthropogenic risk than those recruited for standard monitoring purposes, and juvenile wolves as well as dispersers, succumbed to higher anthropogenic risk. Multivariate models revealed that increasing wolf population density promoted higher anthropogenic risk and reduced natural risk, indicating that partially-compensatory effects of anthropogenic mortality actually became increasingly additive with population density. The observed compensatory mortality and hazard heterogeneity in our study implies that demographic responses to mortality risk may be complex and more subtle than previously thought; the density-dependent effect of anthropogenic mortality portends a stabilizing influence of humans on recovering wolf populations. We conclude that future assessment of the role of anthropogenic mortality should include individual-based hazard estimation as a complement to traditional population-level approaches.     

A multivariable prognostic model for equine colic patients

A survey of 1965 equine colic cases was conducted from August 1985 to July 1986 ten equine referral hospitals located througout the U.S.A. Two-thirds of the cases were randomly selected for model development (1336), while the remaining cases (629) were used only for subsequent validation of the model. The following outcomes were defined: (1) died or killed prior to discharge from the hospital; or (2) alive at the time of discharge. Only variables which were significant (P<0.05) in an initial bivariate screening procedure and for which there were less than 400 missing values were considered in the multivariable modelling. A multivariable logistic regression model was constructed using a stepwise algorithm. The model used 666 cases and included the following variables: peripheral pulse (normal or weak), pulse rate, surgical or medical treatment, packed cell volume, self-inflicted trauma (absent or present) and capillary refill time. For each horse in the validation data set which had the appropriate variables recorded (n=335), the estimated expected probability of death (expected value) was calculated using the logistic regression equation. Using Bayes theorem, the post-test probability was calculated from the expected value (an estimate of the test odds) and the present probability (the case-fatality rate at each institution). Nomograms of predictive values for different case-fatality rates and expected values were constructed. Hosmer-Lemeshow goodness-of-fit statistics indicated that the model fitted the model data set well but the validation set poorly. However, when the observed case-fatality rates were compared with the average post-test probabilities for 0.10 increments of post-test probability, qualitatively, the model's performance was better.     

URETERAL FIBROEPITHELIAL POLYPS IN FOUR DOGS

Four dogs with ureteral fibroepithelial polyps, ranging from 9-12 years of age, are presented in this report. The patients presented with urinary incontinence, urinary tract infection, and/or polydypsia and pollakiuria. All dogs were intact at the time of diagnosis or for the majority of their lives and three were male. Various diagnostic procedures were performed including ultrasonography, contrast radiography, and nuclear scintigraphy. Not all procedures were performed in all patients. Findings included ureteral dilation proximal to the level of an intraluminal mass and ipsilateral hydronephrosis. Unilateral ureteronephrectomy was performed in three dogs with masses in the proximal ureter; ureteral resection and anastamosis was performed in the remaining patient with a mass located in the distal ureter. The same pathologist (RAP) reviewed all four lesions. The lesions appeared polypoid and were attached to the ureteral wall by a thin stalk. Histopathologically, they contained a superficial layer of well-differentiated transitional epithelial cells overlying a prominent fibrovascular stroma with a mild (three dogs) or marked (one dog) degree of lymphoplasmacytic inflammation. This disease may represent a benign neoplasm or a chronic inflammatory reaction and has a good prognosis with surgical removal. Its histopathological characteristics, higher incidence in males, and location more commonly within the upper third of the ureter is remarkably similar to the disease in humans.     

Regulation of muscle differentiation: stimulation of myoblast fusion in vitro by catecholamines

Epinephrine and isoproterenol provoke primary chick myoblasts to initiate precocious cell fusion. Both the rise in intracellular adenosine 3' ,5-monophosphate (cyclic AMP) and cell fusion generated by these effectors are prevented by propranolol, which is a specific blocker of the beta-adrenergic receptor. Propranolol has no effect either on the precocious cell fusion provoked by prostaglandin E or on cell fusion in control cultures. The results support the idea that a rise in cyclic AMP is the critical intracellular change responsible for initiating events that culminate in myoblast differentiation 4 to 5 hours later. They also indicate that the culminate in myoblast differentiation 4 to 5 hours later. They also indicate that the hormone responsible for the positive regulation of myoblast differentiation in vitro is not acting through the beta-adrenergic receptor.     

Production of ethylene by fungi

Ethylene was detected by gas chromatography, and verified by chemical means, as a metabolic product of 22 species of fungi. Because 58 of 228 species of fungi produced a gaseous compound with retention time identical to that of authentic ethylene, we believe that this compound is a common metabolic product of fungi.     

Evidence for chain molecules enriched in carbon, hydrogen, and oxygen in comet halley

In situ measurements of the composition and spatial distribution of heavy thermal positive ions in the coma of comet Halley were made with the heavy-ion analyzer RPA2-PICCA aboard the Giotto spacecraft. Above 50 atomic mass units an ordered series of mass peaks centered at 61, 75, 91, and 105 atomic mass units were observed. Each peak appears to be composed of three or more closely spaced masses. The abundances decrease and the dissociation rates increase smoothly with increasing mass. These observations suggest the presence of chain molecules that are enriched in carbon, oxygen, and hydrogen, such as polyoxymethylene (polymerized formaldehyde), in comet Halley.