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Palmitoylation regulates diverse aspects of neuronal protein trafficking and function. Here a global characterization of rat neural palmitoyl-proteomes identifies most of the known neural palmitoyl proteins-68 in total, plus more than 200 new palmitoyl-protein candidates, with further testing confirming palmitoylation for 21 of these candidates. The new palmitoyl proteins include neurotransmitter receptors, transporters, adhesion molecules, scaffolding proteins, as well as SNAREs and other vesicular trafficking proteins. Of particular interest is the finding of palmitoylation for a brain-specific Cdc42 splice variant. The palmitoylated Cdc42 isoform (Cdc42-palm) differs from the canonical, prenylated form (Cdc42-prenyl), both with regard to localization and function: Cdc42-palm concentrates in dendritic spines and has a special role in inducing these post-synaptic structures. Furthermore, assessing palmitoylation dynamics in drug-induced activity models identifies rapidly induced changes for Cdc42 as well as for other synaptic palmitoyl proteins, suggesting that palmitoylation may participate broadly in the activity-driven changes that shape synapse morphology and function.

Further Observations on Tumour-Enhancing Factors: Their Bearing on the Immunological Theory of Cancer

CLINICAL and pathological observations on Chinese hamsters (Cricetulus griseus) with spontaneous hereditary diabetes mellitus have been reported previously in several papers1–7. Generally speaking, the disease in Chinese hamsters is primarily pancreatogenic, with degranulation, hydropic degeneration and deficiency of β-cells. Other forms of pathological expression noted in symptomatic animals are glomerulosclerosis, arteriosclerosis, increased periodontal breakdown, and proneness toward the formation of adenocarcinomas of the pancreas.

INJECTION of anti-rat-liver serum into rats led to the induction of liver tumour, whereas the injection of anti-serum against 3′-methyl-4-dimethylaminoazobenzene (3′-DAB)-treated rat liver failed to produce any such tumour1. It was postulated that repeated exposures to tissue specific antisera might have induced adaptive loss of tissue specific antigen with malignancy as an essential consequence. It was also thought that the tissue specific antigen was modified by haptenic binding with 3′-DAB, making the antibody against it innocuous to normal liver. The present investigation was undertaken to examine the nature of localization of antibodies against normal and 3–-DAB-treated rat liver, in the liver and other tissues of both normal and 3′-DAB-treated rats.

SEVERAL authors1 have suggested that changes in the immunological reactivity of a cell may be correlated with changes in its surface structure. We present evidence here that human red cells giving a positive antiglobulin reaction show changes in their surfaces demonstrable with the electron microscope.

One in Six An Outline of the Cancer Problem. By Dr. I. Hieger. Pp. 80 + 15 plates. (London: Allan Wingate (Publishers), Ltd., 1955.) 12s. 6d. net.

IT was shown by Green1 and Bielschowsky and Green2 that injection of the sodium salts of adenosine triphosphate, obtained from Dyckerhoff's "myotoxin", into a variety of animals resulted in a shock-like syndrome. It was suggested that the pyrophosphate group might be responsible for at least some of the described effects.

TEN rats were implanted with Walker tumour and on the same day an succeeding days of the experiment the drinking water was replaced by 0.45 per cent hydrogen peroxide as described by Holman1. They all died at the same time (13–14 days) with tumours of the same weight (25–34 gm.) as in the ten control rats. Another transplantable tumour, the Sheffield Rd/3 sarcoma, was also used in an exactly similar experiment except that there were 6 rats per group. In the peroxide group all died at 16–21 days (tumour-weight 38–46 gm.) and in the control group receiving tap water there was one natural regression and the remaining 5 died at 16–21 days (tumour-weight 32–39 gm.). We have had a long experience with the actions of possible chemotherapeutic agents on these tumours, and they are responsive to some of them. We can assert confidently that in the environment of the University of Sheffield Field Laboratories this particular treatment is completely ineffective.

IT has been argued that the concentration of sugar (or glycogen) within a tissue is a critical factor in controlling the rate of mitosis1. An abundance of sugar induces active cell division, while a sugar deficiency results in mitosis depression. Such a depression follows treatment with insulin, which lowers the blood sugar level ; phloridzin, which interferes with phosphorylation ; and starvation, which depletes the carbohydrate reserves of the whole body.

IN the course of experiments designed to test the effect of new cytotoxic chemicals on the Furth leukaemia in the rat, we decided to examine some clinically established cancer chemotherapeutic agents. Because we believed that the action of the agents might have an immunological basis, each was tested alone and in combination with Freund's complete adjuvant.

IN an effort to discover common mechanisms responsible for growth-inhibition of both tissue cells and bacteria, colloidal solutions of carcinogenic compounds (including 1–2–5–6 dibenzanthracene, 3–4 benzpyrene, methylcholanthrene, dimethyl yellow) have been tested systematically by us for possible bacteriostatic action. No very significant results have been obtained.

WHILE investigating the changes in phosphates of muscle in tourniquet shock, Bollman and Flock1 have confirmed and amplified our previous finding (Green)2 by showing that the adenosine triphosphate content of rat muscle falls progressively after clamping of the limb to reach a very low level at the time (four hours) at which, when both limbs are involved, fatal shock develops after release. They conclude that "this type of shock is definitely not due to ATP washed out of the muscle because ATP is destroyed during the occlusion and its decomposition products appear to be relatively non-toxic". In our opinion, the results of Bollman and Flock1 only allow the conclusion that tourniquet shock is not due to a sudden release of adenosine triphosphate into the circulation on removal of the clamp. We never considered it likely that this was the mechanism, since a single dose of adenosine triphosphate injected intravenously produces acute symptoms and not the gradual merging into a shock-like state seen in ischaemic shock and after injection of adenosine triphosphate by routes other than the intravenous2.

DURING recent studies on carbohydrate metabolism in shock, we have examined the citrate-level in the kidney of the fasting rat by Buffa and Peters's modification1 of the method of Pucher, Sherman and Vickery2, during the shock state produced by the parenteral injection of nucleotides. A marked increase (P = 0.01) in the citrate content of the kidney occurred 1 hr. after the intraperitoneal injection of a lethal dose of adenosinetriphosphate (250 mgm. magnesium adenosinetriphosphate per 100 gm. body-weight in the strain of rat used, at an environmental temperature of 18–22° C.; see table). This increase was not maintained, and 4 hr. after the injection the level had returned to normal. In its time relationships this effect resembles that seen in fluoro-acetate poisoning; but in the latter condition the increase in the citrate content of the rat kidney is much greater1,3.

HOWEVER applied, or wherever injected, blastogenic agents, including tar and carcinogenic hydrocarbons, viruses and radium, usually induce in fowls mesoblastic tumours, that is, sarcomata or leukaemias. So far as we are aware, the only exception to this statement are the carcinomata which Japanese workers claimed to have obtained by injecting Scarlet Red and related azo compounds into fowls1,2,3,4.