A conditioned visual orientation requires the ellipsoid body in Drosophila.

Orientation, the spatial organization of animal behavior, is an essential faculty of animals. Bacteria and lower animals such as insects exhibit taxis, innate orientation behavior, directly toward or away from a directional cue. Organisms can also orient themselves at a specific angle relative to the cues. In this study, using Drosophila as a model system, we established a visual orientation conditioning paradigm based on a flight simulator in which a stationary flying fly could control the rotation of a visual object. By coupling aversive heat shocks to a fly's orientation toward one side of the visual object, we found that the fly could be conditioned to orientate toward the left or right side of the frontal visual object and retain this conditioned visual orientation. The lower and upper visual fields have different roles in conditioned visual orientation. Transfer experiments showed that conditioned visual orientation could generalize between visual targets of different sizes, compactness, or vertical positions, but not of contour orientation. Rut-Type I adenylyl cyclase and Dnc-phosphodiesterase were dispensable for visual orientation conditioning. Normal activity and scb signaling in R3/R4d neurons of the ellipsoid body were required for visual orientation conditioning. Our studies established a visual orientation conditioning paradigm and examined the behavioral properties and neural circuitry of visual orientation, an important component of the insect's spatial navigation.

Edge detection depends on achromatic channel in Drosophila melanogaster.

Edges represent important information in object recognition, and thus edge detection is crucial for animal survival. Various types of edges result from visual contrast, such as luminance contrast and color contrast. So far, the molecular and neural mechanisms underlying edge detection and the relationship between different edge information-processing pathways have been largely undemonstrated. In the present study, using a color light-emitting-diode-based Buridan's paradigm, we demonstrated that a blue/green demarcation is able to generate edge-orientation behavior in the adult fly. There is a blue/green intensity ratio, the so-called point of equal luminance, at which wild-type flies did not show obvious orientation behavior towards edges. This suggests that orientation behavior towards edges is dependent on luminance contrast in Drosophila. The results of mutants ninaE(17) and sev(LY3);rh5(2);rh6(1) demonstrated that achromatic R1-R6 photoreceptor cells, but not chromatic R7/R8 photoreceptor cells, were necessary for orientation behavior towards edges. Moreover, ectopic expression of rhodopsin 4 (Rh4), Rh5 or Rh6 could efficiently restore the edge-orientation defect in the ninaE(17) mutant. Altogether, our results show that R1-R6 photoreceptor cells are both necessary and sufficient for orientation behavior towards edges in Drosophila.

Morphological characterization of single fan-shaped body neurons in Drosophila melanogaster.

The fan-shaped body is the largest substructure of the central complex in Drosophila melanogaster. Two groups of large-field neurons that innervate the fan-shaped body, viz., F1 and F5 neurons, have recently been found to be involved in visual pattern memory for "contour orientation" and "elevation" in a rut-dependent manner. The F5 neurons have been found to be responsible for the parameter "elevation" in a for-dependent manner. We have shown here that the F1 neuron also affects visual memory for "contour orientation" in a for-dependent way. With the help of Gal4/UAS and FLP-out techniques, we have characterized the morphological features of these two groups of neurons at single neuron resolution. We have observed that F1 or F5 neurons are groups of isomorphic individual neurons. Single F1 neurons have three main arborization regions: one in the first layer of the fan-shaped body, one in the ventral body, and another in the inferior medial protocerebrum. Single F5 neurons have two arborization regions: one in the fifth layer of the fan-shaped body and the other in the superior medial protocerebrum. The polarity of the F1 and F5 neurons has been studied with the Syt-GFP marker. Our results indicate the existence of presynaptic sites of both F1 and F5 neurons located in the fan-shaped body and postsynaptic sites outside of the fan-shaped body.

Differential roles of the fan-shaped body and the ellipsoid body in Drosophila visual pattern memory.

The central complex is a prominent structure in the Drosophila brain. Visual learning experiments in the flight simulator, with flies with genetically altered brains, revealed that two groups of horizontal neurons in one of its substructures, the fan-shaped body, were required for Drosophila visual pattern memory. However, little is known about the role of other components of the central complex for visual pattern memory. Here we show that a small set of neurons in the ellipsoid body, which is another substructure of the central complex and connected to the fan-shaped body, is also required for visual pattern memory. Localized expression of rutabaga adenylyl cyclase in either the fan-shaped body or the ellipsoid body is sufficient to rescue the memory defect of the rut(2080) mutant. We then performed RNA interference of rutabaga in either structure and found that they both were required for visual pattern memory. Additionally, we tested the above rescued flies under several visual pattern parameters, such as size, contour orientation, and vertical compactness, and revealed differential roles of the fan-shaped body and the ellipsoid body for visual pattern memory. Our study defines a complex neural circuit in the central complex for Drosophila visual pattern memory.

[Therapeutic effect of whole body hyperthermia combined with chemotherapy in patients with advanced cancer].

OBJECTIVE: To determine the short-term efficacy and security of whole body hyperthermia (WBH) combined with chemotherapy for advanced cancer. METHODS: Different chemotherapy regimens were applied in 138 patients with advanced cancer. Among them, 68 patients (Group A) didn't receive any other therapies. The other 70 patients (Group B) received WBH together with chemotherapy. WBH was maintained at 40 degrees C approximately 42 degrees C for 50 approximately 60 min (once or twice every week and 4 times a cycle). RESULTS: In Group A, the rate of complete remission (CR) was 2.9%, partial remission (PR) was 36.8%, stable disease was 35.3%, progressive disease was 25.0%, the overall response rate (CR + PR) was 39.7%; while in Group B, the corresponding figures were 5.7%, 52.9%, 25.7%, 25.0%, and 58.6%, respectively. There was significant difference between the two groups (P < 0.05). The rates of III + IV gastrointestinal tract andmyelosuppression toxicities were 26.5% and 16.2% in Group A, while 27.1% and 18.6% in Group B. No significant difference was found. CONCLUSION: WBH combined with chemotherapy is efficient and safe for advanced cancer, and is worth generalizing extensively.

Determining the structure of an unliganded and fully glycosylated SIV gp120 envelope glycoprotein.

HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 A resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

Structure of an unliganded simian immunodeficiency virus gp120 core.

Envelope glycoproteins of human and simian immunodeficiency virus (HIV and SIV) undergo a series of conformational changes when they interact with receptor (CD4) and co-receptor on the surface of a potential host cell, leading ultimately to fusion of viral and cellular membranes. Structures of fragments of gp120 and gp41 from the envelope protein are known, in conformations corresponding to their post-attachment and postfusion states, respectively. We report the crystal structure, at 4 A resolution, of a fully glycosylated SIV gp120 core, in a conformation representing its prefusion state, before interaction with CD4. Parts of the protein have a markedly different organization than they do in the CD4-bound state. Comparison of the unliganded and CD4-bound structures leads to a model for events that accompany receptor engagement of an envelope glycoprotein trimer. The two conformations of gp120 also present distinct antigenic surfaces. We identify the binding site for a compound that inhibits viral entry.

Crystallization and preliminary diffraction studies of the ectodomain of the envelope glycoprotein D from herpes simplex virus 1 alone and in complex with the ectodomain of the human receptor HveA.

Gycoprotein D (gD) is a glycoprotein expressed on the surface of several human and animal alpha herpes viruses. Binding of gD to cell-surface receptors has been shown to be necessary for herpes simplex virus 1 and 2 (HSV-1 and HSV-2) cell entry. The gD ectodomain consists of 316 residues and has no sequence homology to any other proteins of known structure. Two fragments of the HSV-1 gD ectodomain (gD(22-260): residues 22-260 and gD(285): residues 1-285) have been crystallized in two crystal forms. The complex between gD(285) and the ectodomain of HveA, a gD cellular receptor member of the tumor necrosis factor (TNFR) superfamily, has also been crystallized. Moreover, insect-cell-expressed selenomethionine-substituted gD(285) has been purified and crystallized alone and in complex with HveA.