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The effect of dimethyl sulphoxide and other cryoprotective compounds on the sensitivity of cells to polypeptide toxins and to poliovirus was tested. In the presence of these compounds, which all affect membrane fluidity, the cells were protected against the toxic proteins and against poliovirus. The large protection obtained was not due to reduced binding and endocytosis of the toxins. Apparently, the cryoprotective compounds interfere with the entry of toxins and of the poliovirus genome across the cell membrane.

Toxic proteins in snake venoms are classified according to their principal pharmacological properties as follows : 1) Neurotoxins-postsynaptic neurotoxins from elapid and sea snake venoms and presynaptic neurotoxins from some elapid and crotalus venoms. 2) Myotoxins-Cardiotoxins from elapid venoms and crotamine and other basic proteins from crotalus venoms. 3) Toxic proteins acting on blood vessels and other smooth muscle organs-vasculotoxins, hemorrhagins, and bradykinin-releasing esterases from viperid and crotalid venoms, and phospholipase A from most snake venoms. 4) Local necrotizing agents-proteolytic enzymes from crotalid and viperid venoms and cardiotoxins from elapid venoms. 5) Coagulants-Factor X activators, prothrombin activators and thrombin-like enzymes. 6) Anticoagulantsinactivation of thromboplastin, Factor V and prothrombin, and fibrinolytic enzymes.

Characteristic representatives of the hypersuperfamily comprising digestive enzymes, hormones and a large series of toxins as well as the nodal ancestor of trypsin-related serine proteases and proinsulin have been compared with six unusual (not clearly related) toxins from organisms representing different levels of evolutionary development. In the course of comparison a modification of the previously suggested optimum variant approach is used, making it possible to compare groups of distantly related proteins. A clearly expressed periodicity of the same type is observed in the unusual toxins. The relationship of all proteins examined is established, giving the evolutionary order: serine proteases → proinsulin → toxic proteins.

A large number of sequences of digestive enzymes, hormones and a large series of toxins from organisms representing different levels of evolutionary development have been compared and the results juxtaposed with data about their functions and active sites. This allows random coincidences to be excluded; they serve as a background, against which the real albeit weak analogies are outlined. The results show proinsulin as a protein closest to the common ancestor of the proteins compared. Next in this respect are ribonuclease and phospholipase. It is established that most of the examined proteins are related and constitute a superfamily of a higher level—hypersuperfamily. Evidence in favour of the evolutionary order: cardiotoxins→short and long snake neurotoxins is also presented.

Three proteinase inhibitors, Inhibitor I (a chymotrypsin inhibitor), Inhibitor II (a chymotrypsin and trypsin inhibitor), and Carboxypeptidase Inhibitor were quantified immunologically in extracts of various tissues of Russet Burbank potato tubers and were monitored over various intervals during boiling (30 min), oven baking (80 min, 191°C) and microwave baking (7 min) to assess the effectiveness of cooking in denaturing the potentially toxic proteins. In cooked tubers, Inhibitor II was completely inactivated during all cooking treatments and Inhibitor I was partially inactivated, depending upon the cooking method. The Carboxypeptidase Inhibitor was extraordinarily stable during all of the cooking conditions. Overall, microwave baking was most effective for cumulatively inactivating Inhibitor I and Inhibitor II. The unusual stability of CPI to all types of cooking raises questions concerning the effect of this inhibitor on the total digestibility of cooked potato proteins.

The deoiled meal of tung (Aleurites fordii Hemsl.) kernels is usually a waste because of its toxic effects on livestock, while its oil has some industrial uses. The defatted material was tested for the quantitative levels of common antinutritional factors like tannins and saponins which were found to be 1·55 and 0·72% respectively. The material was tested for detoxification by giving double treatment of rectified spirit followed by 0·2 M sodium hydroxide for a duration of 24 h each. The treated material (containing residual tannins 0·15% and saponins 0·26%) was then tested on one-week-old hybrid male chicks by feeding at 5 and 10% levels for a period of six weeks. The depression in the growth rates was significantly low (P ≤ 0·05) at 10% level of its feeding, while at its 5% level, the growth depression was non-significant. The overall retarded growth syndrome due to this material may be a result of overall affliction of the body metabolism of the experimental chicks, due to the toxic proteins which this material is reported to contain.

Submaxillary gland saliva induced by phenylephrine from male mice was highly toxic to guinea-pigs, rats and hamsters, whereas the toxicity was relatively low to mice. One of the toxic components in the saliva was isolated as a kallikrein-like enzyme.

From an ecological point of view the usage of chemical means for defense or food obtaining purposes may be considered as an efficient and energy saving method. The venom apparatus of scorpions serves as a perfect example of this principle. Scorpions feed on freshly killed prey, consisting of arthropods and generally soft bodied insects. However, as predators, scorpions appear to lack certain essential anatomical and physiological qualities. They move relatively slowly, are practically blind and have a rather undeveloped sense of smell. Scorpions actually do not seek their food actively, but rather wait for the prey to approach their lairs (Bearg, 1961; Stahnke, 1966). Thus, a device for paralyzing the prey at the earliest moment of contact is essential. This is achieved by the venom which is substantially employed for hunting and food obtaining. As we shall see below, this function is associated with highly specified chemical adaptations.

Among the organisms known to produce toxins which inhibit protein synthesis specifically are two pathogenic bacteria, Corynebacterium diphtheriae and Pseudomonas aeruginosa. Although the two pathogens differ markedly in gross characteristics, habitat, transmissibility, and infectious characterisitics, it now seems clear that the major toxic proteins produced by the two have almost identical modes of action at the molecular level. Both catalyze an unusual covalent modification of elongation factor 2 (EF-2), an essential factor in protein synthesis. The factor is thereby inactivated, and protein synthesis is inhibited. This inhibition is believed to be largely or partly responsible for the major toxemic symptoms observed in infections by the two pathogens.

Summary1. Incubation of ferrous sulfate with endotoxin for 6 hours at 37°C prior to injection did not alter the endotoxin-induced-hypersusceptibility-state (EIHS) to water moccasin venom in rabbits. 2. Incubation of ferrous sulfate with snake venom under the same conditions prior to injection gave significant protection against the lethal effects of the venom in endotoxin-pretreated rabbits. 3. Intravenous ferrous sulfate protected a significant number of animals against the lethal effects of snake venom when administered between the preparing endotoxin and the challenging dose of moccasin venom. 4. Prior intravenous ferrous sulfate also resulted in protection against an LD100 of moccasin venom in normal rabbits. 5. Finally, it was shown that administration of large, but non-toxic, doses of ferrous sulfate to endotoxin-pretreated animals resulted in the delayed death of most of the animals.

Two mouse-toxic proteins, Toxin A (240,000 molecular weight) and Toxin B (120,000 molecular weight), were dissociated in sodium dodecyl sulfate to small molecular weight subunits. Subunit size from 10,000 to 12,000 molecular weight is proposed based on gel electrophoresis, ultracentrifugation and dialysis experiments. The subunits retained approximately 60% of the toxic activity of the large molecular weight toxins.

Summary1. Heparin in intravenous doses of 10 to 100 mg counteracted the immediate lethal effects of Russell's viper venom and tiger snake venom in rabbits, but did not prevent the deaths of the animals from the delayed toxic effects of the venom. 2. Heparin in the same intravenous doses did not interfere with the early death that occurs in endotoxin-treated rabbits given Russell's viper venom or tiger snake venom. 3. Heparin neither increased nor decreased the toxicity of moccasin venom in rabbits. 4. Finally, heparin did not affect the EIHS to Agkistrodon piscivorus venom when it was administered before endotoxin, shortly after endotoxin, or just before venom challenge.The authors are greatly indebted to Miss Ann E. Gabrielsen for valuable criticism and advice in the preparation and editing of this work. They also appreciate the technical assistance of Messrs. Nils Rune Forsen, Thomas K. Norrie and Gene Monson.

The crude venoms of the scorpions Androctonus aeneas aeneas , Androctonus amoreuxi , Androctonus mauretanicus mauretanicus , Buthus occitanus pairs , Buthus occitanus tunetanus and Leiurus quinquestriatus were submitted to starch gel zone electrophoresis. The eluates of gel sections were assayed for mice lethality, contraction-paralysis of fly larvae and larvae lethality. It has been found that: (1) All the venoms contain discrete components showing a specific toxicity to mice and to fly larvae. (2) Three of the venoms contain more than one larvae contraction-paralysis component. (3) At pH 8·6, most of the mice toxic components have a cathodic mobility whereas the majority of larvae toxic components migrate towards the anode. (4) All the larvae contraction-paralysis components are strongly lethal to fly larvae and are inactivated by trypsin, thus demonstrating their protein nature. (5) The venoms of A. a. aeneas and B. o. tunetanus contain factions of fast anodic mobility which are lethal to fly larvae but lack the larvae contraction-paralysis and the mice lethal activities. It is concluded that the presence of a variety of toxic proteins specifically active on different animals is a general property of scorpion venoms.

THE paralysing venom of coelenterates is injected into their prey from nematocysts, tiny (55–75 µm) intracellular collagenlike organelles1 found in all members of this phylum2. Recent attempts to investigate the physiological actions of nematocyst venoms3–11,28 have been consistently hampered by (a) the difficulty in obtaining pure undischarged nematocysts free of cytoplasmic contaminants from which the venom could be isolated and (b) the lack of a reliable and accurate physiological assay. The first of these obstacles was overcome by Blanquet and Lenhoff12, who modified a method of Yanagita13 for obtaining extremely pure nematocysts from sea anemone acontia. Acontia are long, thread-like extensions of the gastric filarnents in the gut of certain sea anemones and are laden with nematocysts. From these purified nematocysts, we have isolated two toxic proteins. We describe here three methods of assaying some physiological effects of these proteins.

The Type VI secretion system (T6SS) is a bacterial nanomachine that fires toxic proteins into target cells. Deployment of the T6SS represents an efficient and widespread means by which bacteria attack competitors or interact with host organisms and may be triggered by contact from an attacking neighbor cell as a defensive strategy. Here, we use the opportunist pathogen Serratia marcescens and functional fluorescent fusions of key components of the T6SS to observe different subassemblies of the machinery simultaneously and on multiple timescales in vivo. We report that the localization and dynamic behavior of each of the components examined is distinct, revealing a multi-stage and dynamic assembly process for the T6SS machinery. We also show that the T6SS can assemble and fire without needing a cell contact trigger, defining an aggressive strategy that broadens target range and suggesting that activation of the T6SS is tailored to survival in specific niches.

Many neurodegenerative diseases are related to the propagation and accumulation of toxic proteins throughout the brain. The lesions created by aggregates of these toxic proteins further lead to cell death and accelerated tissue atrophy. A striking feature of some of these diseases is their characteristic pattern and evolution, leading to well-codified disease stages visible to neuropathology and associated with various cognitive deficits and pathologies. Here, we simulate the anisotropic propagation and accumulation of toxic proteins in full brain geometry. We show that the same model with different initial seeding zones reproduces the characteristic evolution of different prionlike diseases. We also recover the expected evolution of the total toxic protein load. Finally, we couple our transport model to a mechanical atrophy model to obtain the typical degeneration patterns found in neurodegenerative diseases.