You Are What you Eat: a Metabolomics Approach to Understanding Prey Responses to Diet-Dependent Chemical Cues Released by Predators.

Prey responses to predator cues are graded in intensity in accordance with the degree of threat presented by the predator. In systems in which prey gather information on predators by using chemicals, prey often respond more to the odor of predators that have consumed conspecifics, as opposed to heterospecifics. We investigated the response of a prey species, the mud crab, Panopeus herbstii, to urine of blue crab, Callinectes sapidus, fed mud crabs or oysters. Behavioral analysis was combined with metabolomics to characterize bioactive deterrents in the urine of predators fed different diets. Urine from blue crabs fed oysters or mud crabs depressed mud crab foraging when presented singly, with the urine derived from a mud crab diet being more potent. The magnitude of foraging depression increased with urine concentration. When urine from blue crabs fed oysters or mud crabs was combined, response to the urine mixture was no different from that to urine derived only from a mud crab diet. Metabolomics analysis indicated diet-dependent differences were related to a set of shared spectral features that differed in concentration in the respective urines, likely consisting of aromatic compounds, amino acids, and lipids. Taken together, these results suggest mud crabs distinguish diet of, and therefore the risk imposed by, predators through detection of a suite of compounds that together represent what the predator has recently consumed.

Neuronal responses to target onset in oculomotor and somatomotor parietal circuits differ markedly in a choice task.

We often look at and sometimes reach for visible targets. Looking at a target is fast and relatively easy. By comparison, reaching for an object is slower and is associated with a larger cost. We hypothesized that, as a result of these differences, abrupt visual onsets may drive the circuits involved in saccade planning more directly and with less intermediate regulation than the circuits involved in reach planning. To test this hypothesis, we recorded discharge activity of neurons in the parietal oculomotor system (area LIP) and in the parietal somatomotor system (area PRR) while monkeys performed a visually guided movement task and a choice task. We found that in the visually guided movement task LIP neurons show a prominent transient response to target onset. PRR neurons also show a transient response, although this response is reduced in amplitude, is delayed, and has a slower rise time compared with LIP. A more striking difference is observed in the choice task. The transient response of PRR neurons is almost completely abolished and replaced with a slow buildup of activity, while the LIP response is merely delayed and reduced in amplitude. Our findings suggest that the oculomotor system is more closely and obligatorily coupled to the visual system, whereas the somatomotor system operates in a more discriminating manner.

Decoding flexion of individual fingers using electrocorticographic signals in humans.

Brain signals can provide the basis for a non-muscular communication and control system, a brain-computer interface (BCI), for people with motor disabilities. A common approach to creating BCI devices is to decode kinematic parameters of movements using signals recorded by intracortical microelectrodes. Recent studies have shown that kinematic parameters of hand movements can also be accurately decoded from signals recorded by electrodes placed on the surface of the brain (electrocorticography (ECoG)). In the present study, we extend these results by demonstrating that it is also possible to decode the time course of the flexion of individual fingers using ECoG signals in humans, and by showing that these flexion time courses are highly specific to the moving finger. These results provide additional support for the hypothesis that ECoG could be the basis for powerful clinically practical BCI systems, and also indicate that ECoG is useful for studying cortical dynamics related to motor function.

Decoding two-dimensional movement trajectories using electrocorticographic signals in humans.

Signals from the brain could provide a non-muscular communication and control system, a brain-computer interface (BCI), for people who are severely paralyzed. A common BCI research strategy begins by decoding kinematic parameters from brain signals recorded during actual arm movement. It has been assumed that these parameters can be derived accurately only from signals recorded by intracortical microelectrodes, but the long-term stability of such electrodes is uncertain. The present study disproves this widespread assumption by showing in humans that kinematic parameters can also be decoded from signals recorded by subdural electrodes on the cortical surface (ECoG) with an accuracy comparable to that achieved in monkey studies using intracortical microelectrodes. A new ECoG feature labeled the local motor potential (LMP) provided the most information about movement. Furthermore, features displayed cosine tuning that has previously been described only for signals recorded within the brain. These results suggest that ECoG could be a more stable and less invasive alternative to intracortical electrodes for BCI systems, and could also prove useful in studies of motor function.

Inhibition of ClC-2 chloride channels by a peptide component or components of scorpion venom.

ClC chloride channels play essential roles in membrane excitability and maintenance of osmotic balance. Despite the recent crystallization of two bacterial ClC-like proteins, the gating mechanism for these channels remains unclear. In this study we tested scorpion venom for the presence of novel peptide inhibitors of ClC channels, which might be useful tools for dissecting the mechanisms underlying ClC channel gating. Recently, it has been shown that a peptide component of venom from the scorpion L. quinquestriatus hebraeus inhibits the CFTR chloride channel from the intracellular side. Using two-electrode voltage clamp we studied the effect of scorpion venom on ClC-0, -1, and -2, and found both dose- and voltage-dependent inhibition only of ClC-2. Comparison of voltage-dependence of inhibition by venom to that of known pore blockers revealed opposite voltage dependencies, suggesting different mechanisms of inhibition. Kinetic data show that venom induced slower activation kinetics compared to pre-venom records, suggesting that the active component(s) of venom may function as a gating modifier at ClC-2. Trypsinization abolished the inhibitory activity of venom, suggesting that the component(s) of scorpion venom that inhibits ClC-2 is a peptide.

Brevetoxin Depuration in Shellfish via Production of Non-toxic Metabolites: Consequences for Seafood Safety and the Environmental Fate of Biotoxins.

During blooms of the dinoflagellate Karenia brevis, filter-feeders such as oysters and clams bioaccumulate brevetoxins, often to levels that are toxic to humans. In controlled aquarium experiments, we exposed live oysters to bloom levels of toxic K. brevis, followed by 10 weeks of exposure to non-toxic microalgae. Oysters were harvested weekly and analyzed for brevetoxins and brevetoxin metabolites to quantify toxin bioaccumulation and depuration. All of the PbTx-2 concentrated by oysters was immediately converted to a mixture of polar metabolites that were then slowly eliminated from the oysters. However, 90% of measured PbTx-3 was eliminated within two weeks of toxic exposure but without apparent biotransformation. Extracts of oysters containing high levels of PbTx-3 were toxic to mice by intraperitoneal (IP) injection. Extracts of oysters harvested after PbTx-3 had been eliminated were non-toxic despite high concentrations of PbTx-2 metabolites. Oysters collected in Florida during and after a bloom of K. brevis contained polar metabolites of PbTx-2 as well as PbTx-3, but no PbTx-2. Again, PbTx-3 concentration was a good predictor of mouse toxicity. One hundred percent conversion of PbTx-2 to polar metabolites was also accomplished in vitro by spiking oyster or clam homogenate with PbTx-2, followed by a brief incubation at room temperature. These PbTx-2 metabolites did not kill mice, either orally or by intraperitoneal injection, even at concentrations 30 times greater than toxic PbTx-3 levels.

[Syndrome of inappropriate antidiuretic hormone secretion in non-differentiated small cell lung cancer]. / Syndrom neprimerené sekrece antidiuretického hormonu u nediferencovaného malobunecného karcinomu plic.

Hyponatraemia is one of the most frequent disorders of the electrolyte metabolism. One of the causes may be also the syndrome of inadequate antidiuretic hormone secretion. The cause of increased production of antidiuretic hormone can be not only a pathological condition affecting the hypothalamo-pituitary system but also ectopic production of antidiuretic hormone or peptide with the same effect on the distal portion of the nephron. A classical type of malignant tumour where the syndrome of inadequate antidiuretic hormone secretion develops is small cell lung cancer. It is also known that some pharmaceutical preparations stimulate the output of antidiuretic hormone or potentiate its effect.

New antifeedant triterpene glycosides from the Caribbean sponge Erylus formosus.

Two groups of antifeedant triterpene glycosides were identified from the Caribbean sponge Erylus formosus. The structure of formoside B, a novel N-acetyl amino derivative of the known penasterol tetrasaccharide formoside, was elucidated using NMR and mass spectral data. Four triterpene hexasaccharides and two triterpene trisaccharides, characterized by a 31-carbon aglycone, proved difficult to isolate and therefore only the structure of their aglycone was determined. Gas chromatographic analysis of derivatized saccharides from these mixtures established the carbohydrate content of these compounds. All of the triterpene glycosides isolated contributed to the chemical defenses of this sponge, although with differing activities.

Two antifeedant lignans from the freshwater macrophyte Saururus cernuus.

Two diarylbutane derivatives of dihydroguaiaretic acid have been isolated from emergent portions of the southeastern United States freshwater angiosperm Saururus cernuus L. (Saururaceae). Bioassay-guided fractionation of organic extracts of S. cernuus led to the compounds, sauriols A and B, in addition to five previously known lignoids. These metabolites deter feeding by the omnivorous crayfish Procambarus clarkii. The two lignans were identified by analysis of nuclear magnetic resonance and mass spectral data, and by comparison with spectral data of dihydroguaiaretic acid.

Evidence for de novo biosynthesis of the polyketide fragment of diaulusterol A by the northeastern pacific dorid nudibranch diaulula sandiegensis

Stable isotope incorporation experiments using sodium [1, 2-13C2]acetate have demonstrated that the 3-hydroxybutyrate substituent of diaulusterol A (1) is biosynthesized de novo by the dorid nudibranch Diaulula sandiegensis. There was no evidence for acetate incorporation into the steroid portion of 1, nor were radiolabeled mevalonate or cholesterol incorporated.

[Molecular biology and serologic analysis in an epidemic of viral hepatitis B in vaccinated patients on hemodialysis]. / Molekulárne-biologická a sérologická analýza epidemie virové hepatitidy B u vakcinovaných hemodialyzovaných pacientu.

The authors analyzed an epidemic of viral hepatitis B during which 43% patients of the hemodialyzation centre in K were infected. Using the method of sequence analysis of the DNA of hepatitis B virus they identified the source of infection. They monitored serologically the course of infection in all infected subjects and the state of specific antibody immunity in patients and staff. 22% infections were manifested clinically and 75% infected HBsAg positive patients developed chronic hepatitis. Although 38 of 42 hemodialyzed patients were vaccinated against hepatitis B, 20 patients lacked anti-HBs antibodies before the epidemic. Only one of the patients without anti-HBs was not infected. In 10 immune patients the rise of antibody levels confirmed that they were also exposed to HBV. The effectiveness of vaccination against VHB in hemodialyzed patients is markedly lower. Vaccination of these patients is an important but only supplementary provision in VHB prevention. Sequence analysis of HBV DNA may be a useful tool of epidemiological analysis.

Quantum pharmacologic studies applicable to the design of anticonvulsants: theoretical conformational analysis and structure-activity studies of barbiturates.

We report the first large-scale systematic quantitative structure-activity relationship (QSAR) study of barbiturates, correlating molecular structures with anticonvulsant activity. To achieve this QSAR study, we devised a four-step strategy. In step 1, an optimal quantum mechanical technique for determining the geometry and shape (conformation) of barbiturates was ascertained; this is the AM1 semiempirical molecular orbital method. In step 2, the AM1 method was used to optimize the structures and molecular properties of 48 barbiturates with varying anticonvulsant activity. In step 3, discriminant analysis and regression analysis statistical calculations were used to correlate the molecular properties of the 48 analogues against maximal electroshock (MES) and subcutaneous metrazol (s.c.Met)-induced seizures. In step 4, the contribution of molecular electrostatic properties to barbiturate anticonvulsant activity was further refined by quantum mechanical derived molecular electrostatic potential (MEP) maps. Using this four-step strategy, we defined the pharmacophore, the portion of a molecule responsible for bioactivity, for anti-MES and anti-s.c.Met activity. For anti-s.c.Met activity, barbiturate lipophilicity and geometry are important considerations; for anti-MES activity, barbiturate topologic and electronic properties have increased relevance.

Studies on lectins. LII. Isolation and characterization of the lectin from rye germ (Secale cereale L.).

Rye germ lectin was isolated by extraction of defatted rye germ, fractionation of the extract by ammonium sulfate precipitation, affinity chromatography of the active substances on chitin-beta-glucan and gel filtration on Sephadex G-50. The lectin shows erythroagglutinating activity at a minimum concentration of 2.5 micrograms/ml. The erythroagglutinating activity is the same against human red blood cells of all types of the ABO system and is inhibited by N-acetyl-D-glucosamine. The lectin has no mitogenic activity against mouse splenic lymphocytes. According to the results of polyacrylamide gel electrophoresis the lectin obtained is a mixture of three very similar isolectins of equal erythroagglutinating activity. Sedimentation analysis indicates homogeneity of the lectin preparation; the molecular weight was 56000 as estimated by sedimentation equilibrium. In the presence of urea and sodium dodecyl sulfate the lectin dissociates into 2 types of subunits with molecular weights of 35000 and 19000. The rye germ lectin contains about 2% of neutral sugar and 1% of D-glucosamine. The amino acid composition of the lectin is characterized by a very high content of glycine and half cystine and a low content of apolar amino acids. N-terminal amino acids of the lectin are apparently blocked.