Efficacy of tumor cell vaccine after incorporating monophosphoryl lipid A (MPL) in tumor cell membranes containing tumor-associated ganglioside

Murine B16 melanoma expresses the ganglioside. GM₃. GM₃ shed from tumor cells is immunosuppressive and promotes tumor growth¹. Reduction or elimination of the shed GM₃ could be therapeutic, and the anti-GM₃ antibodies may reduce and clear the shed ganglioside. To test this hypothesis, mice were challenged with tumor cells, with or without inducing anti-GM₃ antibody response. Since gangliosides are poor immunogens and T-cell independent antigens, an adjuvant (monophosphoryl lipid A (MPL), a non-toxic lipid A ofSalmonella), directed against B-cells, was employed. MPL was incorporated onto liposomes and into the surface membrane of B16 mouse melanoma cells; both are rich in GM₃. C57BL/6J mice immunized with MPL-liposomes or MPL-B16 cells responded with elevated levels of anti-GM₃ IgM. Non-immunized mice or mice immunized with B16 cells alone or ganglioside GM₃ alone (without MPL) elicited poor anti-GM₃ IgM response, confirming the GM₃'s immunologic crypticity and MPL's immunopotentiating effect. MPL's immunopotentiating effect was improved by coupling it to melanoma cell membranes C57BL/6J mice were immunized with irradiated B16 alone or MPL alone or MPL-conjugated irradiated B16. After three weekly immunizations, each mouse received a challenge dose of viable syngeneic B16. Neither MPL alone nor B16 alone had a significant effect on tumor growth or host survival; however, administration of MPL-conjugated B16 cells significantly prevented tumor growth and prolonged survival. Our results indicate that MPL-incorporated B16 cells augment the anti-GM₃ IgM response, which may reverse GM₃-induced immunosuppression by eliminating tumor-derived GM₃, and restore immunocompetence.     

Body size, body composition, and behavior of juvenile Belding ground squirrels

Juvenile Belding ground squirrels were studied in the Sierra Nevada. Females were more trappable, had smaller home ranges, and tended to enter hibernation earlier than males. The primary sex ratio was 1:1. Individuals first emerged from the natal burrow at three to four weeks of age and a body weight of 35 g. Body weight and linear dimensions increased thereafter until hibernation began. Maximum prehibernatory weight of 200 to 260 g was attained at about 12 weeks of age. Prehibernatory fattening began at about six weeks of age. Maximum lipid stores attained weighed about 80 percent of the lean, dry body compartment. Seasonal changes occurred in weight of white and brown fat depots, adrenal glands, spleen, heart, kidneys, liver, and testes. Annual variations in snowpack and emergence schedule caused the reproductive period, and thus phenology of juveniles, to vary by as much as three weeks. The last animals to immerge were unusually small, being from late litters. Nonetheless, they may have had lipid stores sufficient for surviving hibernation.     

Mining patterns of the aspen leaf miner, Phyllocnistis populiella, on its host plant, Populus tremuloides

Feeding behavior of aspen leaf miner ( Phyllocnistis populiella ) larvae on quaking aspen ( Populus tremuloides ) leaves was examined, by using image-analysis software, to determine the pattern and distance of the larvae’s mining trails and measure the surface area of infested leaves and consumed leaf tissue. Mining pathways between hatching and pupation sites were serpentine and generally followed predictable, sequential changes in orientation. This pattern was most obvious in smaller leaves, those with a surface area of about 700 mm 2 or less. In leaves larger than 700 mm 2 , plasticity in mining behavior increased. The serpentine pattern was initiated but became truncated when larvae reached full growth without having to consume all available leaf material. The final phase of the behavioral program was still executed, however, and larvae entered pupation at the usual leaf-edge location. We hypothesize that the serpentine pattern is genetically controlled and that it has been selected for because it promotes efficient consumption of a fixed food supply and ensures a favorable location for pupation, especially when reproductive females oviposit on small leaves. Se examinó el comportamiento alimenticio de la larva del minero de hoja de álamo ( Phyllocnistis populiella ) en las hojas del álamo temblante ( Populus tremuloides ) utilizando software de análisis de imágenes para determinar el patrón y la longitud del rastro de las larvas y medir la superficie de las hojas infestadas y del tejido de hoja consumido. Los rastros del minero entre los sitios de eclosión y los de pupación fueron serpentinos, y en general sus cambios de orientación fueron predecibles y secuenciales. Esto fue más obvio en las hojas pequeñas, aquellas con una superficie de menos de 700 mm 2 . En las hojas con una superficie mayor de 700 mm 2 aumentó la plasticidad en el comportamiento minero. El patrón serpentino apareció al inicio pero se truncó cuando las larvas alcanzaron su pleno desarrollo sin tener que consumir todo el material herbáceo disponible. Sin embargo, la última fase del patrón conductual aún se llevó a cabo, y comenzaron la pupación en el borde de la hoja como de costumbre. Planteamos la hipótesis de que el patrón serpentino tiene origen genético y que ha sido seleccionado a favor porque facilita el consumo eficiente de un suministro fijo de alimento y garantiza un lugar favorable para la pupación, especialmente cuando las hembras reproductoras ovipositan en hojas pequeñas.     

The organs of prey capture and digestion in the miniature predatory bivalve Spheniopsis brasiliensis (Anomalodesmata: Cuspidarioidea: Spheniopsidae) expose a novel life-history trait

Spheniopsis brasiliensis, from depths of 17–148 m off the southern Atlantic coast of Brazil, is a predator of epipsammic micro-crustaceans which it sucks into the infra-septal chamber using a raptorial inhalant siphon and internally generated hydrostatic suction forces. Prey items, which include ostracods, are thought to be pushed into the funnel-shaped mouth using the foot. The stomach is capacious with a short style sac conjoined briefly with the mid gut and possessing a stubby crystalline style. Internal stomach architecture is simplified, with no identifiable sorting areas (unlike other cuspidarioids) and lined virtually completely by a gastric shield. The exoskeletal remains of digested prey are held in the posterior end of the stomach and not in a specialised waste storage pouch as in the con-familial Grippina coronata. The mid gut, hind gut and rectum are all extremely narrow and, thus, only the smallest of faeces can be accommodated and transmitted for anal discharge. Spheniopsis brasiliensis, like G. coronata is a self-fertilising simultaneous hermaphrodite with encapsulated lecithotrophic eggs brooded internally. Both taxa are thus ovovivaporous. It is also believed that both taxa are univoltine so that larvae and the exoskeletal prey remains are all released post mortem. Cuspidariids are generally regarded as dioecious but, recently, Cardiomya costellata has been shown to be a non-brooding simultaneous hermaphrodite. The distinguishing characters between cuspidariids and spheniopsids thus appear to be their differing reproductive strategies and life history traits.     

Microbiological transformation of 6,14-endo-ethenotetrahydrothebaine alkaloids

Zusammenfassung In der vorliegenden Arbeit werden mikrobiologische Umwandlungen von mehreren 6, 14-endo-Äthenotetrahydrothebain Alkaloiden beschrieben. Mit Hilfe von verschiedenen Mikroorganismen konnten stereospezifische Reduktionen undN-Desalkylierungen ausgeführt werden.     

Unexpected inhibition of fusion in nucleus-nucleus collisions

Unstable heavy atomic nuclei not found in nature can be created by fusing two stable nuclei, in a process analogous to colliding charged droplets of liquid. Recently, the formation of a handful of super-heavy nuclei with atomic numbers 114 (ref. 1) and 116 (ref. 2) has been achieved by fusion of heavy nuclei. The electrostatic energy of such systems is very large (which is the reason super-heavy nuclei are unstable), so although the two nuclei may initially be captured by the nuclear potential, rather than fusing, they almost always separate after transfer of mass to the lighter nucleus. This process, called quasi-fission, can inhibit fusion by many orders of magnitude. Understanding this inhibition may hold the key to forming more super-heavy elements. Theoretically, inhibition is predicted (ref. 5 and references therein) when the product Z1Z2 of the charges of the projectile and target nuclei is larger than about 1,600. Here we report measurements of three fusion reactions with Z1Z2 around half this value, each forming 216 88Ra. We find convincing model-independent evidence both of inhibition of fusion, and of the presence of quasi-fission. These results defy interpretation within the standard picture of nuclear fusion and fission.     

Integration of cytogenetic landmarks into the draft sequence of the human genome

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.     

Role of heavy water as solvent in the Antigen-Antibody precipitin reaction

Zusammenfassung Wenn die Lösung zu 50% aus schwerem Wasser bestand, blieb die Bildung von Antigen-Antikörperpräcipitat im Bereich des Antikörperüberschusses unverändert. Dies zeigt, dass die Substitution mit Deuterium die spezifischen Bindungseigenschaften nicht verändert. Dagegen fand sich eine erhöhte Niederschlagsmenge im Bereich des Antigenüberschusses, was auf eine Herabsetzung der Löslichkeit des normalerweise löslichen Antigen-Antikörperkomplexes hinweist.