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Understanding the pathogenesis of herpesvirus of turkeys (HVT) in its natural host is necessary before recombinant HVT (rHVT) can be used efficiently in turkey flocks. The objectives of this study were to evaluate when commercial turkey flocks get infected with wild type HVT, to study replication of HVT (conventional and recombinant rHVT-Newcastle disease, rHVT-ND) and other Marek's disease (MD) vaccines (SB-1 and CVI988) in turkey embryonic tissues, and to evaluate the expression of TLR-3 and IFN-γ in the lung and spleen of one-day-old turkeys after in ovo vaccination with MD vaccines. Our results demonstrated that commercial turkeys got exposed to wild type HVT within the first days of life; therefore, there is a potential of interaction between wild type HVT and rHVT when administered at day of age. On the other hand, all evaluated vaccines (especially HVT and rHVT-ND) replicated very well in turkey embryonic tissues. In ovo vaccination with HVT and CVI988 increased transcription of TLR-3 in the spleen of one-day-old turkeys. However, no effect on the transcription of TLR-3 or IFN-γ in the lungs and IFN-γ in the spleen in newly hatched turkeys was detected in the present study. Because of the limitations of evaluated genes, timepoints, and studied tissues, future studies are warranted to better understand the effect of MD vaccines on the turkey embryo immune responses.RESEARCH HIGHLIGHTS Commercial turkey flocks get infected with wild type HVT within the first days of life.HVT and rHVT replicates readily in turkey embryonic tissues.SB-1 and CVI988 also replicate in turkey embryonic tissues, but at lower rates than HVT and rHVT.HVT and CVI988 increase transcription of TLR-3 in the spleen.

A series of (3R*,4R*)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists with varying substituents on the nitrogen were evaluated for their effect on food consumption in obese Zucker rats. Opioid affinity (mu, kappa, and delta for selected compounds) and opioid antagonist activity (mu and kappa) were characterized and compared to effects on food consumption. No compounds with high selectivity for either mu or kappa receptors were discovered. However, compounds in the series had exceptional potency as opioid antagonists and in reducing food consumption in the obese Zucker rat. In contrast, a few compounds with high potency as opioid antagonists had much weaker potency for inhibiting food consumption. (3R,4R)-3,4-Dimethyl-1-[(3S)-3- hydroxy-3-cyclohexyl-propyl]-4-(3-hydroxyphenyl)piperidine (11,LY255582) emerged as having the best activity profile, both in reducing food consumption and as an opioid antagonist. Compound 11 is a highly potent mu, kappa-, and delta-opioid antagonist with possible clinical utility as an appetite suppressant for weight loss.

The hormone insulin is synthesized in the beta cell of the pancreas as the precursor, proinsulin, where the carboxyl terminus of the B-chain is connected to the amino terminus of the A-chain by a connecting or C-peptide. Proinsulin is a weak insulin agonist that possesses a longer in vivo half-life than does insulin. A form of proinsulin clipped at the Arg65-Gly66 bond has been shown to be more potent than the parent molecule with protracted in vivo activity, presumably as a result of freeing the amino terminal residue of the A-chain. To generate a more active proinsulin-like molecule, we have constructed an "inverted" proinsulin molecule where the carboxyl terminus of the A-chain is connected to the amino terminus of the B-chain by the C-peptide, leaving the critical Gly1 residue free. Transformation of Escherichia coli with a plasmid coding for A-C-B human proinsulin led to the stable production of the protein. By a process of cell disruption, sulfitolysis, anion-exchange chromatography, refolding, and reversed-phase high-performance liquid chromatography, two forms of the inverted proinsulin differing at their amino termini as Gly1 and Met0-Gly1 were identified and purified to homogeneity. Both proteins were shown by a number of analytical techniques to be of the inverted sequence, with insulin-like disulfide bonding. Biological analyses by in vitro techniques revealed A-C-B human proinsulin to be intermediate in potency when compared to human insulin and proinsulin. The time to maximal lowering of blood glucose in the fasted normal rat appeared comparable to that of proinsulin. Additionally, we were able to generate fully active, native insulin from A-C-B human proinsulin by proteolytic transformation. The results of this study lend themselves to the generation of novel insulin-like peptides while providing a simplified route to the biosynthetic production of insulin.

The effects of the phenylpiperidine opioid antagonist, LY255582, on food consumption, water consumption and body weight gain of the meal-fed obese Zucker rat have been determined. A single subcutaneous dose of LY255582 (0.31 mg/kg) decreased food and water consumption of the meal-fed obese rat. LY255582 was effective as an appetite suppressant at lower doses than ephedrine, amphetamine, fenfluramine, naltrexone and nalmefene. Comparison of the relative in vivo biological activity with in vitro receptor binding assays of LY255582 and its stereoisomers shows that the order of the affinity of the mu and kappa opioid receptors correlates well with biological activity. LY255582 is the most biologically effective and has the highest affinity for both receptors. LY255582 administered chronically to meal-fed obese Zucker rats for 68 days at a subcutaneous dose of 0.31 mg/kg significantly reduced food and water consumption and decreased body weight gain during the entire treatment period. There was no development of tolerance to the biological effects of LY255582.

It has been previously demonstrated that non-enzymatic glycosylation and subsequent cross-linking of proteins can occur at high or greater than physiological concentrations of glucose. Soluble collagen was incubated in the presence of increasing glucose concentrations. The amount of cross-linked collagen was determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Our findings reveal that cross-linking due to non-enzymatic glycosylation occurs at or near physiological concentrations of glucose (3.11-4.22 mM). In addition, this glucose induced cross-linking is a time dependent reaction. When collagen was incubated with a variety of different carbohydrates it was found that ketoses are more active cross-linking agents than aldoses. The addition of a reactive group (such as an amine) alpha to the aldehyde group on the carbohydrate increases the cross-linking activity of glucose 2.8 fold. Blockage of the reactive group alpha to the aldehyde (such as N-acetyl glucosamine or 2-deoxy-D-glucose) totally abolishes glycosylation activity. Both 5-C and 7-C carbohydrates are more active than 6-C carbohydrates. Thus, although glucose may be the most abundant carbohydrate capable of non-enzymatic glycosylation and subsequent cross-linking, it is not the most chemically reactive. However, the significance of these findings to the pathogenesis of diabetes needs to be defined.

Meal-fed Zucker rats were used to determine the acute and chronic s.c. effect of certain trans-3,4-dimethyl-4-phenylpiperidines (opioid antagonists) on food consumption. In acute studies, the active compounds suppressed food intake significantly of lean and obese meal-fed Zucker rats. LY117413 was the most effective over the 4-hr period immediately after the s.c. administration of the drug. Long-term chronic s.c. administration to the meal-fed obese Zucker rat showed that LY88329 and LY117413 significantly reduced food consumption for as long as the drug was administered and resulted in a significant decrease in body weight gain when compared to nontreated control obese rats. There was no evidence for the development of tolerance to these effects of LY88329 and LY117413 in this genetically obese rat model.

Off-bottom culture of oysters has attracted great interest by various agencies along the coasts of the United States and Canada. The major commercial interest in off-bottom oyster culture is now centered in the production of seed oysters. The present commercial centers for seed production are: Fishers Island, New York; Dabob Bay, Washington; and Pendrell Sound, British Columbia. At Fishers Island and Pendrell Sound, seed oysters are caught on shells suspended from rafts; in Dabob Bay they are caught on wire-strung shells draped over racks, although some seed is also caught on shells suspended from rafts. Several small companies are rearing oysters (to market size) suspended from rafts and racks, in California, Rhode Island, and Washington. The Bureau of Commercial Fisheries evaluated off-bottom oyster culture at Cape Cod, Massachusetts, in 1956 and is now experimenting with off-bottom culture in artificial ponds, natural ponds, and tributaries of Upper Chesapeake Bay. The present studies include ...

Aeronautics is certainly the science of the future and its professors and preachers have the qualities of their science. When you were good enough to ask me to read a paper, by way of opening a discussion this evening, you told me beforehand the subject which I should select. It is a new departure, characteristic of these new times. If you will look at the practice of education in this or any other country you will find that hitherto subjects have been selected, not by those who are to hear, but by those who are to speak. They are the subjects upon which the teacher has already made up his mind. The principle of selection is that the teacher must be able to display superior knowledge and the process of education is a sort of wave of superior knowledge going down from the universities into the most elementary recesses without much regard for what it looks like from the point of view of those hungry for the knowledge of “how it goes,” and still more “why it goes?” You have provoked this digression by giving me the subject, “Wind Gusts and the Structure of Aerial Disturbances.”

THE report of the work of the cowl committee of the Sanitary Institute presents the results of the numerous experiments made by the committee in the course of upwards of twenty years of its existence—an existence unfortunately terminated by the deaths in rapid succession of all its members. The last survivor, Mr. Rogers Field, B.A., M.Inst.C.E, the most active member of the Committee, died on March 28, 1900.

MR. CAVE'S book is a welcome addition to the valuable contributions of amateurs to the common stock of scientific knowledge, and is the more welcome as the first book on this special subject. The investigation of the upper air is of such interest and the incidental problems which it presents are so numerous, so attractive, and, in these days of flying, so practical, that it is a matter of some surprise that there are not found more men of leisure to follow the notable examples of Prof. Lawrence Rotch and M. Teisserenc de Bort in the Investigation of the free atmosphere. Mr. Cave in his introduction refers to the circumstances in which he began the study of the subject. As a matter of history, they can be traced to a letter by the present writer in The Times asking for the cooperation of yachtsmen in the exploration of the air over the sea by means of kites. Since that letter appeared we have had to chronicle the division of the atmosphere into two distinct layers, an upper layer, the stratosphere, in which there is little or no variation of temperature in the vertical, but sensible variation from day to day, or along the horizontal, and a lower layer, the troposphere, in which the variation of temperature is greatest in the vertical and relatively small along the horizontal. At the boundary between the two layers which is found at different heights in different regions, and on different occasions according to the barometric pressure, there is generally a slight inversion in the fall of temperature with height. Ten kilometres may be taken as a rough and ready estimate of the average thickness of the troposphere with the understanding that there is a latitude of three or more kilometres to be allowed in either direction according to circumstances. The Structure of the Atmosphere in Clear Weather: a Study of Soundings with Pilot Balloons. By C. J. P. Cave. Pp. xii + 144. (Cambridge: The University Press, 1912.) Price 10s. 6d. net.

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Pancreatic islet tissue from lean and obese Zucker rats was investigated with histologic and immunocytochemical techniques, and the changes in cytologic composition were correlated with levels of serum glucose, lipids, and insulin. The insular changes in obese rats progressed in severity with increasing age. Changes consisted of pronounced insulin cell hyperplasia, disarrangement of islet architecture, and disappearance (degranulation?) of a new islet cell type, the pancreatic polypeptide cell. High levels of free fatty acids, triglyceride, and insulin were detected in serum of obese rats. Upon diet restriction, these parameters decreased and islet morphology became normalized. When obese Zucker rats were treated with streptozotocin, high levels of serum free fatty acids and triglycerides remained but there was a great reduction in serum insulin levels to near normal levels. Pancreatic polypeptide cells werenot found in the islets. It is suggested that high free fatty acid and triglyceride levels in obese rats may be related to the inability to demonstrate pancreatic polypeptide cells in the islets of 100- to 300-day-old obese Zucker rats.

MR. MALLOCK'S position in the scientific world is one of distinction and his letters on the subject or weather forecasts in England, which appeared in NATURE of February 26 and June 4, can, accordingly, scarcely fail to be regarded by many who are unfamiliar with the circumstances as reflecting injuriously upon the department of the public service which is in my charge. I ought, therefore, not to let them pass unnoticed.

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No one is more conscious of the shortcomings and omissions of the address than its author. One correction I should like to make here. The joint editors of the Meteorologische Zeitschrift are Dr. Hann and Dr. Hellmann; Dr. Pernter is associated with the journal as “Herausgeber.”

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In February 1905 I made a short communication to the Royal Society of London (Proceedings, Vol. Lxxiv. page 562), upon an apparent relation between the yield of wheat for England in the 21 successive years 1884 to 1904 and the aggregate rainfall for the three autumnal months (September, October, November) of the preceding years of the principal wheat-producing districts of Great Britain. The relation was put into the algebraical form

THE primary difficulty in the way of using science schools, as suggested by Mr. J. V. H. Coates, for the immediate purposes of such an inquiry as that of the distribution of fogs is that the schools have fixed hours of attendance to which the fogs pay no heed. To carry out such an investigation effectively the twenty-four hours must be taken into account. Of course the inquiry might be restricted to those fogs which begin or end within the hours of attendance, but that would be a very serious limitation. As confirmatory evidence, careful observations within school hours might be very useful. The necessity for securing a suitable uniformity among observers as regards the terms employed in the estimation of fogs makes it necessary, however, to proceed with caution in extending the number of separate observers.

THE translation into English of tne first volume of Dr. Hann's “Climatologie” is a very welcome addition to the library of English-speaking meteorologists. The translation does not extend to the last two volumes of the original work, which deal with special climatology, as it has been found “impracticable” to translate them. This is greatly to be regretted, for the generalisations which constitute the science of climatology cannot be satisfactorily treated without reference to the statistical data and the means for verifying them. Moreover, a compendious review, in English, of the statistics of the various meteorological elements arranged according to geographical distribution is constantly wanted for many purposes, and either a translation of Dr. Hann's volumes, or a reproduction in an abridged form of Dr. Buchan's volume of the Challenger reports, is a necessity of which every student of meteorology must be aware. It is quite true that such a survey would be a work of reference, and would not serve as a text-book in a course of general climatology, and as that is Prof. Ward's purpose in preparing the translation, we must unfortunately wait for some other interest to prompt the translation of the two volumes of special climatology.