Sustained Increase In Frequency Research Articles

Spatial and temporal second messenger codes for growth cone turning

Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by axon guidance molecules are unknown. Here, we identify characteristics of cAMP and calcium transients generated in growth cones during Netrin-1-dependent axon guidance. In filopodia, Netrin-1-dependent Deleted in Colorectal Cancer (DCC) receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. In contrast, activation of DCC in growth cone centers leads to a transient calcium-dependent cAMP increase and a sustained increase in frequency of calcium transients. We show that filopodial cAMP transients regulate spinal axon guidance in vitro and commissural axon pathfinding in vivo. These growth cone codes provide a basis for selective activation of specific downstream effectors.

Highlights of This Issue

Aberrant activation of β-catenin contributes to the malignant phenotype of hepatocelluar carcinoma (HCC), but its role in hypoxia remains unclear. Liu and colleagues demonstrate that β-catenin becomes activated in HCC cells in response to hypoxia, regardless of β-catenin mutational status. Activation of β-catenin due to hypoxia had no effect on cell proliferation, but contributed to hypoxia-induced metastatic potential of HCC cells by eliciting epithelial-mesenchymal transition. Further, depletion of β-catenin abrogated the enhanced aggressiveness of HCC caused by hypoxia. These results support using the combination of a β-catenin inhibitor and hypoxia-related therapy for the treatment of HCC.Multiple myeloma (MM) is a B-cell malignancy commonly characterized by chromosomal translocations. In this study, Nakashima and colleagues evaluated KW-2478, a heat shock protein 90 (Hsp90) inhibitor, in MM. By treating MM cells with KW-2478, they found that FGFR3 is a new Hsp90 client protein. They also found that two other Hsp90 client proteins, Cdk9 and phosphorylated 4E-BP1, were depleted following treatment with KW-2478, demonstrating that KW-2478 affects both transcriptional and translational pathways. Studies using an orthotopic mouse model of MM further suggested that KW-2478 could be a promising strategy for the treatment of MM.Near-infrared fluorescence imaging can be used for noninvasive in vivo imaging of tumors. Yang and colleagues demonstrate that a group of heptamethine cyanine dyes have special uptake and retention properties in cancer but not normal cells, mediated by organic anion transporter peptides. They found that these dyes accumulated in human cancer cells, human tumor xenografts, and mouse tumors in transgenic animals without the need for chemical conjugation. The differential accumulation of these dyes in cancer but not normal cells could have clinical utility, including the detection of circulating cancer cells in the blood and of tumor cells in pathologic specimens.Many immunotherapy trials are conducted in the metastatic setting and rely on monitoring of peripheral blood. However, systemic immune responses may not reflect changes within tumors. Here, Carthon and colleagues conducted a preoperative trial with anti–CTLA-4, in which they identified an increased frequency of ICOShi T cells in tumors and blood following treatment. Additional studies in a separate cohort of patients with metastatic disease correlated a sustained increase in frequency of ICOShi T cells with clinical benefit. These results suggest that the preoperative model is a powerful investigational platform that can be used to efficiently guide immune monitoring in the metastatic setting.

The Effects of an Aided Augmentative System on Communication and Speech in a Preschool Child with Developmental Delay: A Case Study

The effect of an aided graphic augmentative communication system on communication and speech in a 4‐year 7‐month‐old child with developmental delay was evaluated in this case study. An alternating treatment design was used across 2 mealtime settings (morning tea and lunch) over a 6‐week period with counterbalancing of aided and unaided conditions. Once graphic symbol use emerged, there were slightly higher levels of unprompted communication and requests in the aided condition and a lower proportion of acts contained nonsymbolic communication. There was also a higher number of different words + symbols used in the aided condition. The introduction of the graphic symbols did not appear to have detrimental effects on speech but there was no evidence of sustained increase in frequency of speech or spoken vocabulary in the aided condition. Substantial increases were noted in the number of unprompted communicative turns and range of total vocabulary over the course of the study in both conditions. The need for further research on the effects of AAC on speech and communication in preschool children is highlighted.

The effects of an aided augmentative system on communication and Speech in a preschool child with developmental delay: A case study

The effect of an aided graphic augmentative communication system on communication and speech in a 4‐year 7‐month‐old child with developmental delay was‐evaluated in this case study. An alternating treatment design was used across 2 mealtime settings (morning tea and lunch) over a 6‐week period with counterbalancing of aided and unaided conditions. Once graphic symbol use emerged, there were slightly higher levels of unprompted communication and requests in the aided condition and a lower proportion of acts contained nonsymbolic communication. There was also a higher number of different words + symbols used in the aided condition. The introduction of the graphic symbols did not appear to have detrimental effects on speech but there was no evidence of sustained increase in frequency of speech or spoken vocabulary in the aided condition. Substantial increases were noted in the number of unprompted communicative turns and range of total vocabulary over the course of the study in both conditions. The need for further research on the effects of AAC on speech and communication in preschool children is highlighted.

Sow behaviour in computerised feeding systems

Computerised dry sow feeding systems are becoming increasingly popular as an alternative to earlier husbandry systems, partly in order to overcome some of the welfare problems associated with tethered sow systems. In order to investigate the feeding behaviour of dry sows in such a system, to see whether it may give rise to any welfare problems of its own, an interface has been developed between a system with two feeding stations (Pig Code) and a microcomputer data collection system recording the amount of food eaten and the time and duration of every visit. Data collected over a 2°month period showed a regular diurnal variation in visits to feeding stations. A peak in visiting frequency coincided with the start of the daily feeding cycle at 07:05 a.m. (GMT). This was composed of a sharp rise in the frequency of non-feeding visits during the 2 h before the start of the feeding cycle, followed by an even sharper and more sustained increase in frequency of feeding visits when the new cycle started. The animals used the two feeding stations to unequal extents. The causes underlying these results have yet to be established. Strategies and Tactics in Foraging of the Eatable The Pursuit A.W. ILLIUS Department of Agriculture, University of Edinburgh, West Mains Road, Edinburgh EH9 3JG (Gt. Britain) ABSTRACT Optimal foraging theory provides a framework for the analysis of foraging behaviour. Foraging strategies are part of a hierarchy of strategic goals which contribute eventually to the lifetimeOptimal foraging theory provides a framework for the analysis of foraging behaviour. Foraging strategies are part of a hierarchy of strategic goals which contribute eventually to the lifetime