Thomas Hunt Morgan

HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use.

To study HIV-1 escape from a coreceptor antagonist, the R5 primary isolate CC1/85 was passaged in peripheral blood mononuclear cells with increasing concentrations of the CCR5-specific small molecule inhibitor, AD101. By 19 passages, an escape mutant emerged with a >20,000-fold resistance to AD101. This virus was cross-resistant to a related inhibitor, SCH-C, and partially resistant to RANTES but still sensitive to CCR5-specific mAbs. The resistant phenotype was stable; the mutant virus retained AD101 resistance during nine additional passages of culture in the absence of inhibitor. Replication of the escape mutant in peripheral blood mononuclear cells completely depended on CCR5 expression and did not occur in cells from CCR5-Δ32 homozygous individuals. The escape mutant was unable to use CXCR4 or any other tested coreceptor to enter transfected cells. Acquisition of CXCR4 use is not the dominant in vitro escape pathway for a small molecule CCR5 entry inhibitor. Instead, HIV-1 acquires the ability to use CCR5 despite the inhibitor, first by requiring lower levels of CCR5 for entry and then probably by using the drug-bound form of the receptor.

Evolution and adaptation

Post-visit Links and Activities After visiting Jordan Halls vivarium, bird and specimen collections, and greenhouse at Indiana University, you and your students may want to know more! Here are some links, on-line activities, and places to visit where you can continue exploring evolution. Web Resources: 1. This website has lots of great lessons, demonstrations, articles, and links on the nature of science, evolution, origins and genetics. 2. This website is from HHMI and is an excellent source of well-researched, widely accepted scientific information. It is highly interactive with lectures, articles, animations, activities and videos. 3. This site has articles from many different sources. It presents a wealth of information on all of the most common questions about evolution. There are lots of links within the articles too for those who want to know more on a particular idea. 4. This web site goes through the evolution of flight and how different animals arrived at similar, but unique answers to natures challenge of getting off the ground. 6. Indiana state parks are a great place to observe the diversity of plants and animals. Fossils can be studied at many of Indianas state parks as well. Several parks have programs covering topics related to evolution.

Chromosomes and Heredity

WE have come to look upon the problem of heredity as identical with the problem of development. The word heredity stands for those properties of the germ-cells that find their expression in the developing and developed or-ganism. When we speak of the transmission of characters from parent to offspring, we are speaking metaphorically; for we now realize that it is not characters that are transmitted to the child from the body of the parent, but that the parent carries over time material common to both parent and offspring. This point of view is so generally accepted to-day that I hesitate to restate it. It will serve at least to show that in what I am about to say regarding. heredity and the germu-cells I shall ignore entirely the possibility that characters first acquired by the body are transmitted to the germ. Were there sufficient evidence to establish this view, our problem would be affected in so far as that we should not omnlv have to account for the way in which the fertilized eggu produces the characters of the adult, but also for the way iu which the characters of the adult modify the germ-cells. Time modern literature of development anmd heredity is permeated through and through by two contending or contrasting views as to how the germ produces the char-

Genetics and the Physiology of Development

THE Sedgwick Lecture, given this year at Woods Hole, where physiologists, embryologists and even geneticists are foregathered, seems a suitable occasion to discuss some of the problems common to the three fields of research. For another reason, too, the occasion seems propitious. Professor Sedgwick, to whose memory these lectures are dedicated, always took a very broad interest in physiology. This interest extended beyond the field of traditional human physiology into the widest biological aspect of physiology, both theoretical and practical. The modern theory of genetics may seem, at first sight, to concern itself with methods quite foreign to those of physiology. Genetics deals with ratios between classes of related individuals that appear in successive generations in crosses between two types differing in one or more characters. There is nothing in this procedure that seems to appeal to physiological processes in the individuals in question-in fact, it seems rather to ignore them. That the process of segregation and crossing-over, as interpreted in terms of chromosome maneuvers, is, in the ultimate analysis, the outcome of physiological processes

The fertilization of non-nucleated fragments of Echinoderm-eggs

Summary1.Non-nucleated fragments of the egg fertilized by one spermatozoon may segment and such pieces have been found as late as the 16-cell-stage.2.Some of the fragments were large enough, judging from the results of the development of nucleated fragments, to produce “partial larvae”.3.The spermatozoa of Echinus enter with the same difficulty the non-nucleated fragments of Sphaerechinus that they do the nucleated fragments and whole eggs.4.The crossed larvae of Sphaerechinus and Echinus (and also Strongylocentrotus lividus and Sphaerechinus) show a great amount of variability in the skeleton.5.Amongst the crossed larvae a large percentage of forms showing the pure Echinus-type of skeleton will be found. The same resultSeeliger has obtained.6.The results taken all together do not exclude the possibility ofBoveris experiment, but they show thatBoveris conclusion rests on insufficient and unsound evidence.Zusammenfassung1.Kernlose Eifragmente, monosperm befruchtet, vermögen sich zu furchen, und zwar wurde Furchung bis zu 16 Zellen an ihnen beobachtet.2.Einige dieser Stücke hatten die Größe von Fragmenten, welche, wenn kernhaltig, noch normale kleine Larven liefern.3.Die Spermatozoa von Echinus dringen in kernlose Eifragmente von Sphaerechinus ebenso schwer ein, wie in kernhaltige Fragmente oder in ganze Eier desselben.4.Die Bastardlarven von Sphaerechinus-Echinus (wie von Sphaerechinus-Strongylocentrotus) sind in ihrer Skeletbildung sehr variabel.5.Unter denselben finden sich viele mit reinem Echinustypus, wie auchSeeliger gezeigt hat.6.Alle diese Resultate zusammengenommen zeigen, dassBoveris Versuch zwar nicht von vorn herein unmöglich, aber in seiner jetzigen Gestalt auf ungenügende und falsche Schlussfolgerungen basirt ist.

Studies of the ‘Partial’ larvae of sphaerechinus

Zusammenfassung1.Das Volumen der kleinsten aus Eifragmenten erhaltenen Gastrulae beträgt weniger als 1/64 vom Volumen normaler Gastrulae. Das Volumen von Eifragmenten, welche solche Gastrulae producirten, schwankt zwischen 1/40 und 1/50 vom Eivolumen.2.Die Zahl der Zellen in Blastulis, welche aus Eifragmenten erhalten sind, steht im Verhältnis zur Größe der Blastula, indem die Grenze der Theilbarkeit jeder Zelle durch das Verhältnis von Kern zu Protoplasma bestimmt ist.3.In kleinen Blastulis sind auch die Kerne kleiner als in normalen Blastulis, die definitive Größe der Zellen ist wahrscheinlich auch kleiner als normaler Weise.4.Eine isolirte Blastomere des Zweizellenstadiums bildet eine Blastula mit der Hälfte der normalen Zellenzahl, eine Blastomere des Vierzellenstadiums ergiebt ein Viertel der normalen Zahl der Zellen oder etwas mehr, und eine solche des Achterstadiums kann zwar 1/8 der normalen Zahl produciren, bildet aber meist mehr. Die isolirten Blastomeren des 2-, 4- und 8-zelligen Stadiums bilden sämmtlich ganz kleine Gastrulae.5.Fragmente der Blastulawandung bilden, wieDriesch gezeigt hat, Gastrulae. Die Zahl der Zellen in solchen Gastrulis steht im Verhältnis zur Größe der Fragmente.6.Die kleinen aus Eifragmenten erhaltenen Blastulae bilden die normale Zahl von Entodermzellen ohne Beziehung zur Größe der Blastula oder zur Zahl ihrer Zellen.7.Der Grund für das Unvermögen isolirter Blastomeren von späterem als dem achtzelligen Stadium, gastrulae zu bilden, liegt darin, dass solche Blastomeren unfähig sind, die für das nächste ontogenetische Stadium nöthige Anzahl von Zellen zu produciren.

The relation of the first plane of cleavage and the grey crescent to the median plane of the embryo of the frog

Summary1)When the first plane of cleavage coincides with the median plane of the grey crescent, the median plane of the embryo coincides with these two. li]2)|When the first plane of cleavage is at right angles to the median plane of the grey crescent, the median plane of the embryo usually coincides either with the first plane of cleavage or with the median plane of the grey crescent, but sometimes with neither. li]3)|The dorsal lip of the blastopore appears on the grey crescent side of the egg. li]4)|In fifty percent of the cases the first plane of cleavage coincides with the median plane of the grey crescent. In about eight and a half per cent of the cases the second plane of cleavage coincides with the median plane of the grey crescent.In the remaining eggs, the first plane of cleavage lies to one side, or the other, of the middle of the grey crescent, usually near to it. li]5)|The smallest black Gell of the four at the eight cell stage always lies on the crescent side of the egg. When the crescent is bisected by the first cleavage plane, the smallest cell lies in eighteen percent to the right, and in twenty-nine percent to the left. When the first cleavage plane does not bisect the crescent, the smallest cell lies nearest the centre of the crescent.Zusammenfassung1)Fällt die erste Theilungsebene mit der Medianebene des grauen Feldes zusammen, dann stimmt auch die Medianebene des Embryo mit diesen beiden überein. li]2)|Steht die erste Theilungsebene rechtwinkelig zu der Medianebene des grauen Feldes, so fällt die Medianebene des Embryo gewöhnlich mit der einen von beiden zusammen, manchmal jedoch mit keiner von beiden. li]3)|Die dorsale Blastoporuslippe erscheint an derselben Seite des Eies, wie das graue Feld. li]4)|In 50% der Fälle fällt die erste Theilungsebene mit der Medianebene des grauen Feldes zusammen. In ungefähr 8 1/2% ist dies mit der zweiten Theilungsebene der Fall.Bei dem Rest der Eier liegt die erste Theilungsebene auf der einen oder der anderen Seite von der Mitte des grauen Feldes, gewöhnlich nahe derselben. li]5)|Die kleinste der vier schwarzen Zellen auf dem Achtzellenstadium liegt stets auf der Feldseite des Eies. Wird das Feld durch die erste Theilungsebene des Eies in zwei Theile getheilt, so liegt die kleinste Zelle in 18% der Fälle rechts, in 27% links. Theilt die erste Theilungsebene das graue Feld jedoch nicht, so liegt die kleinste Zelle ganz nahe dem Centrum des Feldes.