Predictability of visual perturbation during locomotion: implications for corrective efference copy signaling

In guiding adaptive behavior, efference copy signals or corollary discharge are traditionally considered to serve as predictors of self-generated sensory inputs and by interfering with their central processing are able to counter unwanted consequences of an animal??s own actions. Here, in a speculative reflection on this issue, we consider a different functional role for such intrinsic predictive signaling, namely in stabilizing gaze during locomotion where resultant changes in head orientation in space require online compensatory eye movements in order to prevent retinal image slip. The direct activation of extraocular motoneurons by locomotor-related efference copies offers a prospective substrate for assisting self-motion derived sensory feedback, rather than being subtracted from the sensory signal to eliminate unwanted reafferent information. However, implementing such a feed-forward mechanism would be critically dependent on an appropriate phase coupling between rhythmic propulsive movement and resultant head/visual image displacement. We used video analyzes of actual locomotor behavior and basic theoretical modeling to evaluate head motion during stable locomotion in animals as diverse as Xenopus laevis tadpoles, teleost fish and horses in order to assess the potential suitability of spinal efference copies to the stabilization of gaze during locomotion. In all three species, and therefore regardless of aquatic or terrestrial environment, the head displacements that accompanied locomotor action displayed a strong correlative spatio-temporal relationship in correspondence with a potential predictive value for compensatory eye adjustments. Although spinal central pattern generator-derived efference copies offer appropriately timed commands for extraocular motor control during self-generated motion, it is likely that precise image stabilization requires the additional contributions of sensory feedback signals. Nonetheless, the predictability of the visual consequences of stereotyped locomotion renders intrinsic efference copy signaling an appealing mechanism for offsetting these disturbances, thus questioning the exclusive role traditionally ascribed to sensory-motor transformations in stabilizing gaze during vertebrate locomotion.     

Object localization through the lateral line system of fish: theory and experiment

Fish acquire information about their aquatic environment by means of their mechanosensory lateral-line system. This system consists of superficial and canal neuromasts that sense perturbations in the water surrounding them. Based on a hydrodynamic model presented here, we propose a mechanism through which fish can localize the source of these perturbations. In doing so we include the curvature of the fish body, a realistic lateral line canal inter-pore distance for the lateral-line canals, and the surface boundary layer. Using our model to explore receptor behavior based on experimental data of responses to dipole stimuli we suggest that superficial and canal neuromasts employ the same mechanism, hence provide the same type of input to the central nervous system. The analytical predictions agree well with spiking responses recorded experimentally from primary lateral-line nerve fibers. From this, and taking into account the central organization of the lateral-line system, we present a simple biophysical model for determining the distance to a source.     

Identification of epitopes recognized by monoclonal antibodies directed against HTLV-I envelope surface glycoprotein using peptide phage display

Summary Phage peptide libraries constitute powerful tools for the mapping of epitopes recognized by monoclonal antibodies (mAbs). Using screening of phage displayed random peptide libraries we have characterized the binding epitopes of three mAbs directed against the surface envelope glycoprotein (gp46) of the human T-cell leukemia virus type I (HTLV-I). Two phage libraries, displaying random heptapeptides with or without flanking cysteine residues, were screened for binding to mAbs 7G5D8, DB4 and 4F5F6. The SSSSTPL consensus sequence isolated from constrained heptapeptide library defines the epitope recognized by DB4 mAb and corresponds to the exact region 249–252 of the virus sequence. The APPMLPH consensus sequence isolated from non constrained heptapeptide library defines the epitope recognized by 7G5D8 mAb and corresponds to the region 187–193 with a single amino acid substitution, methionine to leucine at position 190. The third consensus sequence LYWPHD isolated from constrained heptapeptide library defines the epitope recognized by 4F5F6 mAb. It corresponds to an epitope without direct equivalence with the virus sequence. The data presented here showed that 7G5D8 and DB4 mAbs are raised against linear epitopes while 4F5F6 mAb recognized a continoous topographic epitope.     

Nucleotide sequence of the Acinetobacter calcoaceticus trpGDC gene cluster

A plasmid library of Acinetobacter calcoaceticus HindIII fragments was constructed, and clones that complemented an Escherichia coli pabA mutant were selected. Plasmids containing a 3.9-kb fragment of A. calcoaceticus DNA that also complemented E. coli trpD and trpC-(trpF+) mutants were obtained. We infer that complementation of E. coli pabA mutants was the result of the expression of the amphibolic anthranilate- synthase/p-aminobenzoate-synthase glutamine-amidotransferase gene and that the plasmid insert carried the entire trpGDC gene cluster. In E. coli minicells, the plasmid insert directed the synthesis of polypeptides of 44,000, 33,000, and 20,000 daltons, molecular masses that are consistent with the reported molecular masses of phosphoribosylanthranilate transferase, indoleglycerol-phosphate synthase, and anthranilate-synthase component II, respectively. A 3,105- bp nucleotide sequence was determined. Comparison of the A. calcoaceticus trpGDC sequences with other known trp gene sequences has allowed insight into (1) the evolution of the amphibolic trpG gene, (2) varied strategies for coordinate expression of trp genes, and (3) mechanisms of gene fusions in the trp operon.      

Design,synthesis, docking,Hirshfeld surface analysis and DFT calculations of 2-methylxanthen-9-with the FtsZ protein from Staphylococcus aureus

It is of interest to document the design, synthesis, docking, Hirshfeld surface analysis and DFT calculations of 2-methylxanthen-9-with the FtsZ protein (PDB ID: 3VOB) from Staphylococcus aureus for antimicrobial applications. We report the quantitative structure function data in this context.     

Lateral line nerve fibers do not code bulk water flow direction in turbulent flow

The discharges of anterior and posterior lateral line nerve afferents were recorded while stimulating goldfish, Carassius auratus, with bulk water flow. With increasing flow velocity lateral line afferents increased their discharge rates. However, an increased response to flow rates occurred even if flow direction was reversed. Thus, individual lateral line afferents did not encode the direction of running water. Frequency spectra of the water motions quantified with particle image velocimetry revealed flow fluctuations that increased with increasing flow velocity. Maximal spectral amplitudes of the flow fluctuations were below 5 Hz (bulk flow velocity 4–15 cm s⁻¹). The frequency spectra of the firing rates of lateral line afferents also showed an increase in amplitude when fish were exposed to running water. The maximal spectral amplitudes of the recorded data were in the frequency range 3–8 Hz. This suggests that the lateral line afferents mainly responded to the higher frequency fluctuations that developed under flow conditions, but not to the direct current flow or the lower frequency fluctuations. Although individual lateral line afferents encoded neither flow velocity nor flow direction we suggest that higher order lateral line neurons can do so by monitoring flow fluctuations as they move across the surface of the fish.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone, (HDMP) to prevent ‘trafficking’ of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the ‘blood brain barrier (BBB)’. Three men with newly diagnosed PCNSL, ages 62, 76 and 78 y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin’s lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70 y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.     

Autoantibodies directed against membrane phospholipid in serum in patients with malignant tumors

Modifications of membrane lipids in the levels of fatty acids and phospholipids are associated with malignant tumors. In order to evaluate if these changes are recognized by the immune system, we have attempted to assay the possible presence of autoantibodies directed against the following lipids: phosphatidylinositol (PI), phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, gangliosides, galactocerebrosides, sphingomyelin, sphingosin, and cardiolipin, in the sera of patients with malignant tumors (n = 324) and from controls [healthy subjects (n = 20) and patients suffering of other diseases (n = 60)]. Using an adaptated immunoenzymatic assay (ELISA method), a highly significant difference (p less than 0.001) was found between the mean absorbances read on the cancer and control group for only one lipid, the PI. Whatsmore, these auto anti-PI were found in all sera (diluted 15,000 times) of patients with malignant tumors, whatever type, grade, or organ localization defined. These data indicated that the immune system recognized the PI antigenic modifications which appear to be linked to the cell transformation. This PI-immunological binding may have a predictive value as we have recently noticed in animals bearing chemically-induced malignant tumors.     

Response properties of electrosensory neurons in the lateral mesencephalic nucleus of the paddlefish

Many fishes and amphibians are able to sense weak electric fields from prey animals or other sources. The response properties of primary afferent fibers innervating the electroreceptors and information processing at the level of the hindbrain is well investigated in a number of taxa. However, there are only a few studies in higher brain areas. We recorded from electrosensory neurons in the lateral mesencephalic nucleus (LMN) and from neurons in the dorsal octavolateral nucleus (DON) of the paddlefish. We stimulated with sine wave stimuli of different amplitudes and frequencies and with moving DC stimuli. During sinusoidal stimulation, DON units increased their firing rate during the negative cycle of the sine wave and decreased their firing rate to the positive cycle. Lateral mesencephalic nucleus units increased their rate for both half cycles of the sine wave. Lateral mesencephalic nucleus units are more sensitive than DON units, especially to small moving dipoles. Dorsal octavolateral nucleus units respond to a moving DC dipole with an increase followed by a decrease in spike rate or vice versa, depending on movement direction and dipole orientation. Lateral mesencephalic nucleus units, in contrast, increased their discharge rate for all stimuli. Any change in discharge rate of DON units is converted in the LMN to a discharge rate increase. Lateral mesencephalic nucleus units therefore appear to code the presence of a stimulus regardless of orientation and motion direction.