The responses of Limulus optic nerve fibers to patterns of illumination on the receptor mosaic

The inhibition that is exerted mutually among receptor units (ommatidia) of the compound eye of Limulus is less for units widely separated than for those close together. This diminution of inhibition with distance is the resultant of two factors: (1) the threshold of inhibitory action increases with increasing distance between the units involved; and (2) the coefficient of inhibitory action decreases with increasing distance. The discharge of nerve impulses from ommatidia at various distances from one another may be described quantitatively by a set of simultaneous linear equations which express the excitatory effects of the illumination on each ommatidium and the inhibitory interactions between each ommatidium and its neighbors. The values of the thresholds and coefficients of inhibitory action, which appear as parameters in these equations, must be determined empirically: their dependence on distance is somewhat irregular and cannot yet be expressed in an exact general law. Nevertheless the diminution of inhibitory influences with distance is sufficiently uniform that patterns of neural response generated by various patterns of illumination on the receptor mosaic can be predicted qualitatively. Such predictions have been verified experimentally for two simple patterns of illumination: an abrupt step in intensity, and a simple gradient between two levels of intensity (the so-called Mach pattern). In each case, transitions in the pattern of illumination are accentuated in the corresponding pattern of neural response.     

Inhibition of immune aggregate-induced activation of the first complement component by cationic polypeptides

A cationic amino acid copolymer (CP530) with a molar ratio of lysine, leucine, tryptophan and phenylalanine of 11:2:1:1 and a M_r of about 2300 was prepared and its inhibitory effects on the complement cascade was compared with those of polylysine with a M_r of about 3000. The effects of these two cationic peptides appeared to be at the early stage of complement activation. CP530 and polylysine inhibited the binding of C1q to insoluble IgG aggregates with a concentration required for 50% inhibition of 0.7 and 0.9 mM, respectively. Both compounds were also potent inhibitors of immune hemolysis (a concentration causing 50% inhibition, 0.5 and 3.5 μM respectively) as well as well as assembly of EAC cell intermediates required for formation of C3 and C5 convertases (a concentration for 50% inhibition of 1.0 μM for CP530 and 3.8 μM for polylysine). However, CP530 was shown to be distinctly more effective against the activation of C1r·Cls complex induced by insoluble IgG aggregate-bound C1q, requiring 0.15 mM for 50% inhibition compared to greater than 10 mM for polylysine. The 50% inhibition value for soluble IgG aggregate-induced activation of C1 in whole serum was 0.7 mM for CP530 and 5.0 mM for polylysine. The greater the inhibition of C1 activation by CP530 than that exerted by polylysine could be attributable to the presence of non-lysyl residues which provide the structural basis for specificity and potency.     

Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats

Cathinone, the main bioactive alkaloid of Catha edulis (khat), slightly increased the blood sugar levels of healthy animals, while its effect on blood sugar levels of diabetic animals has not yet been reported. This study investigated the in vitro inhibition of cathinone on α-amylase and α-glucosidase as well as its in vivo glycemic effects in diabetes-induced rats. Rats were fed on a high fat diet for five weeks, which then intraperitoneally injected with streptozotocin (30 mg/kg). Diabetic rats were distributed randomly into diabetic control (DC, n = 5), 10 mg/kg glibenclamide-treated group (DG, n = 5), and 1.6 mg/kg cathinone-treated group (CAD, n = 5). Additional healthy untreated rats (n = 5) served as a nondiabetic negative control group. Throughout the experiment, fasting blood sugar (FBS), caloric intake and body weight were recorded weekly. By the 28th day of treatment, rats were euthanized to obtain blood samples and pancreases. The results demonstrated that cathinone exerted a significantly less potent in vitro inhibition than α-acarbose against α-amylase and α-glucosidase. As compared to diabetic control group, cathinone significantly increased FBS of diabetic rats, while insulin levels of diabetic rats significantly decreased. In conclusion, cathinone was unable to induce a substantial in vitro inhibition on α-amylase and α-glucosidase, while it exacerbated the hyperglycemia of diabetes-induced rats.     

The effects of paraquat on Escherichia coli:Distinction between bacteriostasis and lethality

Paraquat exerted a progressively more pronounced bacteriostatic effect on Escherichia coli as its concentration was raised in the range 0–1.0 μM. In contrast, concentrations of 100 μM or greater were required before significant lethality could be observed. This bacteriostatic effect of paraquat could be eliminated by supplementation of the glucose-plus-salts medium with either yeast extract or a casein hydrolysate. This protection was seen whether the supplement was added a few minutes prior to or following the addition of paraquat and was thus not due to the inhibition of active uptake of paraquat by the cells. The lethal effect of high levels of paraquat was not influenced by supplementation of the medium with yeast extract. It follows that the bacteriostatic and lethal effects of paraquat involve attack upon distinct targets within the cell.     

Inhibitory interaction of receptor units in the eye of Limulus

The inhibition that is exerted mutually among the receptor units (ommatidia) in the lateral eye of Limulus has been analyzed by recording oscillographically the discharge of nerve impulses in single optic nerve fibers. The discharges from two ommatidia were recorded simultaneously by connecting the bundles containing their optic nerve fibers to separate amplifiers and recording systems. Ommatidia were chosen that were separated by no more than a few millimeters in the eye; they were illuminated independently by separate optical systems. The frequency of the maintained discharge of impulses from each of two ommatidia illuminated steadily is lower when both are illuminated together than when each is illuminated by itself. When only two ommatidia are illuminated, the magnitude of the inhibition of each one depends only on the degree of activity of the other; the activity of each, in turn, is the resultant of the excitation from its respective light stimulus and the inhibition exerted on it by the other. When additional receptors are illuminated in the vicinity of an interacting pair too far from one ommatidium to affect it directly, but near enough to the second to inhibit it, the frequency of discharge of the first increases as it is partially released from the inhibition exerted on it by the second (disinhibition). Disinhibition simulates facilitation; it is an example of indirect effects of interaction taking place over greater distances in the eye than are covered by direct inhibitory interconnections. When only two interacting ommatidia are illuminated, the inhibition exerted on each (decrease of its frequency of discharge) is a linear function of the degree of activity (frequency of discharge) of the other. Below a certain frequency (often different for different receptors) no inhibition is exerted by a receptor. Above this threshold, the rate of increase of inhibition of one receptor with increasing frequency of discharge of the other is constant, and may be at least as high as 0.2 impulse inhibited in one receptor per impulse discharged by the other. For a given pair of interacting receptors, the inhibitory coefficients are not always the same in the two directions of action. The responses to steady illumination of two receptor units that inhibit each other mutually are described quantitatively by two simultaneous linear equations that express concisely all the features discussed above. These equations may be extended and their number supplemented to describe the responses of more than two interacting elements.     

A Novel Neurotoxin from Venom of the Spider,Brachypelma albopilosum

Spiders have evolved highly selective toxins for insects. There are many insecticidal neurotoxins in spider venoms. Although a large amount of work has been done to focus on neurotoxicity of spider components, little information, which is related with effects of spider toxins on tumor cell proliferation and cytotoxicity, is available for Brachypelma albopilosum venom. In this work, a novel spider neurotoxin (brachyin) was identified and characterized from venoms of the spider, Brachypelma albopilosum. Brachyin is composed of 41 amino acid residues with the sequence of CLGENVPCDKDRPNCCSRYECLEPTGYGWWYASYYCYKKRS. There are six cysteines in this sequence, which form three disulfided bridges. The serine residue at the C-terminus is amidated. Brachyin showed strong lethal effects on American cockroaches (Periplaneta americana) and Tenebrio molitor (common mealbeetle). This neurotoxin also showed significant analgesic effects in mice models including abdominal writhing induced by acetic acid and formalin-induced paw licking tests. It was interesting that brachyin exerted marked inhibition on tumor cell proliferation.     

An ALS-Linked Mutant SOD1 Produces a Locomotor Defect Associated with Aggregation and Synaptic Dysfunction When Expressed in Neurons of Caenorhabditis elegans

The nature of toxic effects exerted on neurons by misfolded proteins, occurring in a number of neurodegenerative diseases, is poorly understood. One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons. We report on effects of an ALS-associated, misfolding-prone mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans. Stable mutant transgenic animals, but not wild-type human SOD1 transgenics, exhibited a strong locomotor defect associated with the presence, specifically in mutant animals, of both soluble oligomers and insoluble aggregates of G85R protein. A whole-genome RNAi screen identified chaperones and other components whose deficiency increased aggregation and further diminished locomotion. The nature of the locomotor defect was investigated. Mutant animals were resistant to paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal sensitivity to the cholinergic agonist levamisole and normal muscle morphology. When fluorescently labeled presynaptic components were examined in the dorsal nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions were observed in mutant animals and brightness was also diminished. At the EM level, mutant animals exhibited a reduced number of synaptic vesicles. Neurotoxicity in this system thus appears to be mediated by misfolded SOD1 and is exerted on synaptic vesicle biogenesis and/or trafficking.     

C-terminal Peptides of Tissue Factor Pathway Inhibitor Are Novel Host Defense Molecules

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the “classic” human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.     

Modulation of Hydra Attentuata rhythmic activity

Here we analyse the previous results concerning the effects of photic and electric stimulation on the contraction-relaxation behaviour of Hydra, the existence of a potential difference between the two extremities of the animal, its rhythmic variation in time, its modulation by luminous environmental changes as well as the contraction pulse variations dependent on the luminous stimulation itself and the complex overt behaviour of an electrically stimulated animal. A model of the mechanism responsible for the rhythmic activity, which takes into account the above results as well as the already known anatomical and physiological data, is given. This model is based on the mutual inhibitory interaction of the two pacemaker systems responsible for the contraction and relaxation outputs, on the post inhibitory rebound after the received inhibition, which rebound constitutes the activity phase of each of them, and on the different weight of the activity exerted by each of them.     

Effect of minor components of virgin olive oil on topical antiinflammatory assays

Interest in the health-promoting effects of virgin olive oil, an important part of the "Mediterranean diet", prompted us to determine the antiinflammatory effects of erythrodiol, beta-sitosterol and squalene, identified as major components of the so-called "unsaponifiable fraction" of virgin olive oil, as well as of the phenolic compounds from the "polar fraction": oleuropein, tyrosol, hydroxytyrosol and caffeic acid. Their activities were compared to those of both, total unsaponifiable and polar fractions. This study was designed to analyse the antiinflammatory effect of these specific compounds from virgin olive oil on edema in mice induced by either arachidonic acid (AA) or 12-O-tetradecanoylphorbol acetate (TPA). The inhibition of the myeloperoxidase (MPO), marker enzyme of the accumulation of neutrophils in the inflamed tissue, was also investigated by the TPA model. The topical application of the olive oil compounds (0.5 mg/ear) produced a variable degree of antiinflammatory effect with both assays. In the auricular edema induced by TPA, beta-sitosterol and erythrodiol from the unsaponifiable fraction of the oil showed a potent antiedematous effect with a 61.4% and 82.1% of inhibition respectively, values not very different to that of the reference indomethacin (85.6%) at 0.5 mg/ear. The four phenolics exerted a similar range of inhibition (33-45%). All compounds strongly inhibited the enzyme myeloperoxidase, indicating a reduction of the neutrophil influx in the inflamed tissues. The strongest inhibitor of AA edema was the total unsaponifiable fraction which inhibition was 34%, similar to that obtained by the reference drug dexamethasone at 0.05 mg/ear. Among the phenolics, oleuropein also produced an inhibition of about 30% with the same dose, but all the other components were found less active in this assay. The anti-inflammatory effects exerted by both unsaponifiable and polar compounds might contribute to the potential biological properties reported for virgin olive oil against different pathological processes.     

4-O-methylhonokiol inhibits colon tumor growth via p21-mediated suppression of NF-κB activity

Biphenolic components in the Magnolia family have shown several pharmacological activities such as antitumor effects. This study investigated the effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, on human colon cancer cell growth and its action mechanism. 4-O-methylhonokiol (0–30 μM) decreased constitutive activated nuclear factor (NF)-κB DNA binding activity and inhibited growth of human colon (SW620 and HCT116) cancer cells. It also caused G₀–G₁ phase cell cycle arrest followed by an induction of apoptotic cell death. However, knockdown with small interfering RNA (siRNA) of p21 or transfection with cyclin D1/Cdk4 binding site-mutated p21 abrogated MH-induced cell growth inhibition, inhibition of NF-κB activity as well as expression of cyclin D1 and Cdk4. Conversely, inhibition of NF-κB with specific inhibitor or siRNA augmented MH-induced apoptotic cell death. 4-O-methylhonokiol inhibited tumor growth, NF-κB activity and expression of antiapoptotic proteins; however, it increased the expression of apoptotic proteins as well as p21 in xenograft nude mice bearing SW620 cancer cells. The present study reveals that MH causes p21-mediated human colon cancer cell growth inhibition through suppression of NF-κB and indicates that this compound by itself or in combination with other anticancer agents could be useful for the treatment of cancer.     

Soil microorganisms interacting with residue-derived allelochemicals effects on seed germination

Despite the knowledge regarding allelopathy, known as a major ecological mechanism for biological weed control, had increased greatly, the role of soil microorganisms in that field remained controversial. The study sought to evaluate the interference potential of soil microorganisms, residues-derived allelochemicals and their interaction on seed germination and understand the variation of microbial community in allelopathic activities. Three different rice residues-derived fractions from variety PI312777 (extracts, straw fraction and fresh residue) were applied to sterile and live soils to disentangle the interference potential of soil microorganisms, residues-derived allelochemicals and their interaction concerned allelopathic activities. The results demonstrated that microbe-only and residues-only exerted onefold promotion and inhibition effects on lettuce (Lactuca sativa Linn.) seed germination, respectively, whereas, microbe-by-residues interaction showed an inhibition at the beginning, and a feeble promotion later. The 20 most dominant genera of microbes were classified into three clusters, with 13 genera in one cluster, only 1 in the second cluster and 6 in the third one. The genera in the first cluster commonly exerted negative effects on phenol content, while showed positive correlation with seed germination. Interestingly, Bacillus, clustered in the second cluster, had an opposite effect alone. The third cluster genera somehow had a weak correlation with both germination as well as the release of the allelochemicals. Overall, we incorporated molecular methodology for tracking bacterial impacts during incubation with allelochemicals, and demonstrated the mutable role of soil microbes in allelopathy. It may be potentially important for stimulating the beneficial roles of microbes for environmentally friendly weed management.     

Learning of visual cues in the fruit fly parasitoid Psyttalia concolor (Szépligeti) (Hymenoptera: Braconidae)

Parasitoids can learn to associate information from the host microhabitat with ovipositional experiences. Psyttalia concolor (Szépligeti) is a koinobiont larval-pupal endoparasitoid of many tephritids. In P. concolor, the role of visual cues learning during host microhabitat location has not been greatly explored. Here, the innate preferences of P. concolor for colours, shapes and patterns were investigated, as well as the effects of sensitisation and associative learning regarding female preferences for these visual cues. Na?ve females showed no innate preferences for a particular colour, shape or pattern, and their responses were unaffected by sensitisation. In contrast, P. concolor females developed clear preferences after training on Ceratitis capitata larvae associated with a given colour, but not when they were trained on different shapes or patterns. Our findings on how P. concolor learn to pick up visual cues could help to define its optimal environment, and to predict its natural post-release distribution in biological control programs.     

Synthesis and inhibitory effect of cis-guggulsterone on lipopolysaccharide-induced production of nitric oxide in macrophages

Guggulsterone is a bioactive plant sterol naturally found in migratory plants. It exists in various forms, and its active compounds include the isomers cis-guggulsterone (E-GS) and trans-guggulsterone (Z-GS). In this study, the anti-inflammatory effects of these two isomeric pregnadienedione steroids were investigated against lipopolysaccharide-induced inflammatory reaction in RAW264.7 mouse macrophages. Our results showed that both guggulsterones inhibited the production of NO in macrophages treated with lipopolysaccharide, with IC50 values ranging from 3.0 to 6.7 μM. E-GS exerted higher efficacy than Z-GS, and its anti-inflammatory effects was mediated through inhibition of iNOS and COX-2 expression.     

Überprüfung von Steuerungssystemen zur Strophenanwahl der Amsel durch digitale Simulierung

Output analysis and input-output experiments had given evidence for five sequential effects occuring independently of each other in the singing behavior of blackbirds (Fig.1). Recently these investigations resulted in a model which summarized the interaction of five functional components evaluated from the found effects; thereby the model explained the data processing controlling the sequential patterning of the behavior (Fig. 2) — During the investigations reported here, this model and alternative models were tested by means of computer programs. Main question: Would the models generate sequences of patterns equivalent to the sequence of vocal patterns produced by a blackbrid? Results:

1. Only the original one of the tested models generated sequences of patterns showing the specific regularities and their characteristic variations corresponding to natural blackbird songs. This brought evidence for a multiplicative mode of interaction between the “component of throttling-back” (Drosselungskomponente) and the other four components; furthermore for a terminal functioning of the “extreme-value-passage” (Extremwertdurchlaß) (Figs, 2–4 and 10).
2. Concerning the “component of periodicity” (Periodikkomponente) the mechanism of a “reset of periods” was falsified while the mechanism of a “continued periodicity” could be made evident. This implied: The periodicity of the single pattern (phrase) runs over the course of the whole song: the proceeding of the oscillation takes place with each output realisation (Fig. 5).
3. Variations of values of the particular parameters given to the different components during the testing programs showed that a) extreme values resulted in “unnatural” sequences of patterns; b) only values lying within distinct intervals generated sequences containing the whole set of the postulated effects; c) exactly with those parameter values, with which one of the effects could get produced in a natural form, also the other effects were generated correspondingly optimal (Figs. 6–8).
4. The differential variation of the values of the particular parameters given to the components (during the testing programs) allowed a lot of predictions concerning the consequences of increasings or decreasings in the strength of the different components. These predictions have to be tested by experiments with natural systems (blackbirds) (Fig. 9; Tables 1–3).

     

Anti-inflammatory and wound healing potential of cashew apple juice (Anacardium occidentale L.) in mice

Cashew apple is a tropical pseudofruit consumed as juice due to its excellent nutritional and sensory properties. In spite of being well known for its important antioxidant properties, the cashew apple has not been thoroughly investigated for its therapeutic potential. Thereby, this study evaluated the antioxidant capacity, anti-inflammatory, and wound-healing activities of cashew apple juice. Juices from ripe and immature cashew apples were analyzed for antioxidant, anti-inflammatory, and wound-healing properties. Those were evaluated in murine models of xylene-induced ear edema and wound excision. Swiss mice were treated with cashew juice by gavage. Edema thickness was measured and skin lesions were analyzed by planimetry and histology. Both antioxidant content and total antioxidant activity were higher in ripe cashew apple juice (RCAJ) than in unripe cashew apple juice (UNCAJ). The UNCAJ presented the main anti-inflammatory activity by a significant inhibition of ear edema (66.5%) when compared to RCAJ (10%). Moreover, UNCAJ also showed the best result for wound contraction (86.31%) compared to RCAJ (67.54%). Despite of higher antioxidant capacity, RCAJ did not promote better anti-inflammatory, and healing responses, which may be explained by the fact that treatment increased antioxidants level leading to a redox “imbalance” turning down the inflammatory response modulation exerted by reactive oxygen species (ROS). The results suggest that UNCAJ presents a greater therapeutic activity due to a synergistic effect of its phytochemical components, which improve the immunological mechanisms as well as an optimal balance between ROS and antioxidants leading to a better wound healing process.     

Effects of Thymus revolutus Célak essential oil and its two major components on Hep G2 cells membrane

In this study pro/anti-oxidant activities of Thymus revolutus Célak (T. revolutus C.) essential oil and its two main components on Hep G2 cells were determined. Twelve components were identified in T. revolutus C. essential oil by GC and GC-MS and the main components of the oil were cymene (32.57%) and γ-terpinene (17.18%). The essential oil showed more cytotoxicity than its two main components on Hep G2 after 24, 48 and 72 hours incubations. Membrane damage effects of the essential oil and its two main components on Hep G2 cells were increased by incubation with IC₁₀, IC₅₀ and IC₇₀ concentrations. Lower essential oil (<IC₅₀) concentrations had cytoprotective and membrane protective effects against H₂O₂. The free radical scavenging activity of the essential oil of T. revolutus C. (EC₅₀ = 250±0.2 μg/mL) was superior to its two main components (neither not active). Oxidation of linoleic acid was effectively inhibited by T. revolutus C. (72.8%), while inhibition values of linoleic acid oxidation were calculated as 23.4.% and 26.7% for cymene and Γ-terpinene, respectively. These findings suggest that essential oils and its two main components had both pro-oxidant and protective (antioxidant) effects and they exhibited those effects depending on concentration.     

Spectral polymorphisms in angiosperm flowers determined by differential ultraviolet reflectance

The ultraviolet reflectance pattern of flowers from 54 species representing 22 families, many native or introduced to Japan, were surveyed. Their differential ultraviolet patterns, i.e. spectral polymorphisms, were recorded by paired photographs of fresh flowers: one taken in full sunlight and the other through a visible spectrum absorbing filter. The different types of polymorphisms observed varied from total absorption by the whole flower to limited absorption by selected floral parts, such as corolla bases (nectar guides) or anthers. Some visible spectrum polymorphisms, e.g. inAnemone andHepatica, were not associated with different ultraviolet patterns. In three species ofIris, a distinct ultraviolet absorbing landing spot and nectar, tunnel guide as well as reflecting anthers are reported. The downward exerted anthers ofSolanum nigrum which shed pollen through bee wing vibration were ultraviolet absorbent. The implications of these ultraviolet patterns for biochemical (flavonoid), taxonomic, pollination and eco-evolutionary research are discussed. Attention is drawn to the seasonal distribution of ultraviolet radiation in the northern hemisphere and its selective role on northern floras.