Monogamy on the fast track

Social monogamy has evolved multiple times and is particularly common in birds. It is not well understood why some of these species are continuously and permanently paired while others occasionally 'divorce' (switch partners). Although several hypotheses have been considered, experimental tests are uncommon. Estrildid finches are thought to be permanently paired because being short-lived opportunistic breeders, they cannot afford the time to form a new pair relationship. Here it is shown through a controlled experimental manipulation that zebra finches (Taeniopygia guttata) allowed to remain with their partners to breed again are faster to initiate a clutch (by approx. 3 days) than birds separated from their mates that have to re-pair, supporting the hypothesis that continuous pairing speeds up initiation of reproduction, a benefit of long-term monogamy in a small, short-lived, gregarious species.     

Synaptic homeostasis on the fast track

Synaptic homeostasis is a phenomenon that prevents the nervous system from descending into chaos. In this issue of Neuron, Frank et al. overturn the notion that synaptic homeostasis at Drosophila NMJs is a slow developmental process. They report that postsynaptic changes are offset within minutes by a homeostatic increase in neurotransmitter release that requires the presynaptic Ca(2+) channel Cacophony.     

Towards a molecular understanding of Drosophila hearing

The Drosophila auditory system is presented as a powerful new genetic model system for understanding the molecular aspects of development and physiology of hearing organs. The fly's ear resides in the antenna, with Johnston's organ serving as the mechanoreceptor. New approaches using electrophysiology and laser vibrometry have provided useful tools to apply to the study of mutations that disrupt hearing. The fundamental developmental processes that generate the peripheral nervous system are fairly well understood, although specific variations of these processes for chordotonal organs (CHO) and especially for Johnston's organ require more scrutiny. In contrast, even the fundamental physiologic workings of mechanosensitive systems are still poorly understood, but rapid recent progress is beginning to shed light. The identification and analysis of mutations that affect auditory function are summarized here, and prospects for the role of the Drosophila auditory system in understanding both insect and vertebrate hearing are discussed.     

Mouse phenogenomics: the fast track to "systems metabolism"

With the completion of the many genomes, genetics is positioned to meet physiology. In this review, we summarize the coming of "systems metabolism" in mammals through the use of the mouse, as a model system to study metabolism. Building on mouse genetics with increasingly sophisticated clinical and molecular phenotyping strategies has enabled scientists to now tackle complex biomedical questions, such as those related to the pathogenesis of the common metabolic disorders. The ultimate goal of such strategies will be to mimic human metabolism with the click of a mouse.     

Effect of "fast track" admission for acute myocardial infarction on delay to thrombolysis.

OBJECTIVE--To evaluate the impact of a fast track triage system for patients with acute myocardial infarction. DESIGN--Comparison of delays in admission to hospital and in receiving thrombolytic treatment before and after introducing fast track system with delays recorded in 1987-8. Patients fulfilling clinical and electrocardiographic criteria for myocardial infarction were selected for rapid access to the cardiac care team, bypassing evaluation by the medical registrar. SETTING--Major accident and emergency, cardiac and trauma centre. SUBJECTS--359 patients admitted to the cardiac care unit during 1 February to 31 July 1990 with suspected acute infarction. MAIN OUTCOME MEASURES--Accuracy of diagnosis and delay from arrival at hospital to thrombolytic treatment. RESULTS--248 of the 359 patients had myocardial infarction confirmed, of whom 127 received thrombolytic treatment. The fast track system correctly identified 79 out of 127 (62%) patients who subsequently required thrombolytic treatment. 95% (79/83) of patients treated with thrombolysis after fast track admission had the diagnosis confirmed by electrocardiography and enzyme analysis. The median delay from hospital admission to thrombolytic treatment fell from 93 minutes in 1987-8 to 49 minutes in fast track patients (p less than 0.001). Delay in admission to the cardiac care unit was reduced by 47% for fast tract patients (median 60 minutes in 1987-8 v 32 minutes in 1990, p less than 0.001) and by 25% for all patients (60 minutes v 45 minutes, p less than 0.001). CONCLUSION--This fast track system requires no additional staff or equipment, and it halves inhospital delay to thrombolytic treatment without affecting the accuracy of diagnosis among patients requiring thrombolysis.     

Hair cell heterogeneity and ultrasonic hearing: recent advances in understanding fish hearing

The past decade has seen a wealth of new data on the auditory capabilities and mechanisms of fishes. We now have a significantly better appreciation of the structure and function of the auditory system in fishes with regard to their peripheral and central anatomy, physiology, behaviour, sound source localization and hearing capabilities. This paper deals with two of the newest of these findings, hair cell heterogeneity and the detection of ultrasound. As a result of this recent work, we now know that fishes have several different types of sensory hair cells in both the ear and lateral line and there is a growing body of evidence to suggest that these hair cell types arose very early in the evolution of the octavolateralis system. There is also some evidence to suggest that the differences in the hair cell types have functional implications for the way the ear and lateral line of fishes detect and process stimuli. Behavioural studies have shown that, whereas most fishes can only detect sound to 1-3 kHz, several species of the genus Alosa (Clupeiformes, i.e. herrings and their relatives) can detect sounds up to 180 kHz (or even higher). It is suggested that this capability evolved so that these fishes can detect one of their major predators, echolocating dolphins. The mechanism for ultrasound detection remains obscure, though it is hypothesized that the highly derived utricle of the inner ear in these species is involved.     

Mechanism of microtubule-facilitated "fast track" nuclear import

Although the microtubule (MT) cytoskeleton has been shown to facilitate nuclear import of specific cancer-regulatory proteins including p53, retinoblastoma protein, and parathyroid hormone-related protein (PTHrP), the MT association sequences (MTASs) responsible and the nature of the interplay between MT-dependent and conventional importin (IMP)-dependent nuclear translocation are unknown. Here we used site-directed mutagenesis, live cell imaging, and direct IMP and MT binding assays to map the MTAS of PTHrP for the first time, finding that it is within a short modular region (residues 82-108) that overlaps with the IMPβ1-recognized nuclear localization signal (residues 66-108) of PTHrP. Importantly, fluorescence recovery after photobleaching experiments indicated that disruption of the MT network or mutation of the MTAS of PTHrP decreases the rate of nuclear import by 2-fold. Moreover, MTAS functions depend on mutual exclusivity of binding of PTHrP to MTs and IMPβ1 such that, following MT-dependent trafficking toward the nucleus, perinuclear PTHrP can be displaced from MTs by IMPβ1 prior to import into the nucleus. This is the first molecular definition of an MTAS that facilitates protein nuclear import as well as the first delineation of the mechanism whereby cargo is transferred directly from the cytoskeleton to the cellular nuclear import apparatus. The results have broad significance with respect to fundamental processes regulating cell physiology/transformation.     

Cochlear function: hearing in the fast lane.

The cochlea amplifies sound over a wide range of frequencies. Outer hair cells have been thought to play a mechanical part in this amplification, but it has been unclear whether they act rapidly enough. Recent work suggests that outer hair cells can indeed work at frequencies that cover the auditory range.     

Neuroethology of ultrasonic hearing in nocturnal butterflies (Hedyloidea)

Nocturnal Hedyloidea butterflies possess ultrasound-sensitive ears that mediate evasive flight maneuvers. Tympanal ear morphology, auditory physiology and behavioural responses to ultrasound are described for Macrosoma heliconiaria, and evidence for hearing is described for eight other hedylid species. The ear is formed by modifications of the cubital and subcostal veins at the forewing base, where the thin (1–3 μm), ovoid (520 × 220 μm) tympanal membrane occurs in a cavity. The ear is innervated by nerve IIN1c, with three chordotonal organs attaching to separate regions of the tympanal membrane. Extracellular recordings from IIN1c reveal sensory responses to ultrasonic (>20 kHz), but not low frequency (<10 kHz) sounds. Hearing is broadly tuned to frequencies between 40 and 80 kHz, with best thresholds around 60 dB SPL. Free flying butterflies exposed to ultrasound exhibit a variety of evasive maneuvers, characterized by sudden and unpredictable changes in direction, increased velocity, and durations of ∼500 ms. Hedylid hearing is compared to that of several other insects that have independently evolved ears for the same purpose-bat detection. Hedylid hearing may also represent an interesting example of evolutionary divergence, since we demonstrate that the ears are homologous to low frequency ears in some diurnal Nymphalidae butterflies.     

Radiation-force assisted targeting facilitates ultrasonic molecular imaging

Ultrasonic molecular imaging employs contrast agents, such as microbubbles, nanoparticles, or liposomes, coated with ligands specific for receptors expressed on cells at sites of angiogenesis, inflammation, or thrombus. Concentration of these highly echogenic contrast agents at a target site enhances the ultrasound signal received from that site, promoting ultrasonic detection and analysis of disease states. In this article, we show that acoustic radiation force can be used to displace targeted contrast agents to a vessel wall, greatly increasing the number of agents binding to available surface receptors. We provide a theoretical evaluation of the magnitude of acoustic radiation force and show that it is possible to displace micron-sized agents physiologically relevant distances. Following this, we show in a series of experiments that acoustic radiation force can enhance the binding of targeted agents: The number of biotinylated microbubbles adherent to a synthetic vessel coated with avidin increases as much as 20-fold when acoustic radiation force is applied; the adhesion of contrast agents targeted to alpha(v)beta3 expressed on human umbilical vein endothelial cells increases 27-fold within a mimetic vessel when radiation force is applied; and finally, the image signal-to-noise ratio in a phantom vessel increases up to 25 dB using a combination of radiation force and a targeted contrast agent, over use of a targeted contrast agent alone.     

A nonuniform sampling approach for fast ultrasonic flow imaging.

Conventional Pulsed Wave Doppler (PWD) systems acquire an ensemble of N echoes per beam line at a constant pulse repetition frequency fprf, so that the pulse repetition interval equals Tpri = 1/fpn. The total time span determines the velocity resolution, and Tpri the unambiguous velocity range. The ensemble size N is by approximation inversely proportional to the frame rate, assuming that the system performs interleaving. For a given frame rate, a tradeoff can only be made between velocity resolution and velocity range. We propose an approach that allows increasing velocity resolution or range while keeping the frame rate constant. The approach is based on nonuniform sampling, i.e. sampling with varying sampling intervals. Thus, for a given ensemble size N a larger total time span, which would increase velocity resolution, or a shorter minimal Tpn, which would increase the velocity range, may be chosen. The conventional Doppler signal processing techniques are not compatible with nonuniform sampling. We, therefore, developed a velocity estimation algorithm for arbitrary sampling that is based on cross correlation. Furthermore, an adaptive wall filter was implemented that differentiates between tissue motion and blood flow. The new approach was successfully tested with in vitro and in vivo data.